Terms in this set (963)
biological psychology AKA behavioural neuroscience
the study of biological bases of phychological processes and behaviour
the study of the nervous system
immune system affects behaviour and
neurons or nerve cells are the basic unit of the
nervous system (speicalized for communication and you have about 100-150 billion)
axons and dendrites
are specialized extensions of neurons that send and recieve info from neurons
are areas where billions of neurons make electrical and chemical contact with eachother - there are trillions
brain has no ___ receptors
why study the brain?
lrg portion of the pop has a disorder of the brain- looking to understand and treat
how fast do electrical impulses travel?
See table 1.1
for comparissons of research perspectives
how can behaviour be described?- one component of five research perspectives
in terms. of 'acts' or processes, or in terms of results or functions
ex) Arm movements can be described according to the muscles that contract or by what the arm is being used for
Species can be compared to study evolution of brain and behaviour:
of behaviour and biological processes because of common ancestry—> tool use in humans and monkeys
Species can be compared to study evolution of brain and behaviour:
in behaviour and biology that have evolved as adaptations to a particular environmental niche.
a trait that is passed on from a common ancestor is __
similarities in solutions can arise ...
independent of each other (for e.g. the wings of a butterfly--took advantage in environmental niche e.g. mating and the wings of a bat-- take advantage of flying bugs their new niche).
Can studying the alcohol preferences of flies help to understand the basis of alcoholism in humans?
yes- some flies are sensitive to ethanol and some are not we can use this study to compare their genes with humans
Can model aspects of depression in rats to understand if similar processes are at play in humans
e.g. rats will exhibit depressive symptoms like not swimming if put in water
Can study dogs to understand the basis of narcolepsy.
transfer to REM sleep- pass out if they get excited
is the process of growing up and growing old.
Behaviours that change over the life span are studied to learn about
functions and mechanisms.
E.g., sexual behaviour is only displayed by mature rodents; can study changes in the brain at puberty to understand how they regulate mating behaviour.
what mechanisms underlie all behaviour
-Neuronal activity is studied to understand how this contributes to behaviour; take a 'reductionist' approach; e.g., memory
-Research can be applied to humans, especially in diseases of the brain;e.g., memory and PTSD (very common in soldiers after war- enviromental stimuli can trigger memory- ketamine has resetting affect on people with PTSD
breaks a system down into its smaller parts, in order to understand it from the bottom up.
THREE APPROACHES TO RELATE BRAIN AND BEHAVIOR: somatic intervention
alteration of a structure or function to see how behaviour is altered.
is the factor that is manipulated
is what is measured in response to changes in from the independent variable
give an example of somatic intervention manipulating the body to affect behaviour
-administer hormone---> strengthening of mating behaviour
doctors disconnected the frontal lobe to put patients in a vegetative state
Walter JAckson freeman the third
performed orbital lobotomy in his van
THREE APPROACHES TO RELATE BRAIN AND BEHAVIOUR: behavioural intervention
intervention in a behaviour to see how structure or function is altered.
Behaviour is then the independent variable and body changes are dependent variables.
example of experiences affecting the body (incl. brain)
put male in presence of female--> changes in hormone levels
while playing music muscicians....
have lower brain activity than non musicians because higher brain activity is associated with unknown tasks but if the tasks become routine then you have lower activity
THREE APPROACHES TO RELATE BRAIN AND BEHAVIOUR: correlation
measures how much a body measure varies with a behavioural measure—but correlation does not imply causation.
example of correlation- body and behavioural measure covary
brain size<<----->> learning scores
neuroplasticity/ neural plasticity
describes the ability of the brain to be changed by environment and by experience.
This can occur during development as well as in adulthood.
Dendritic spines in the brain can change shape in response to stimuli.
Do social interaction result in brain changes?
In rats, social isolation leads to changes in the amygdala (shrinkage). Amgydala processes emotional simuli
A brain region involved with processing odours, the posterodorsal amygdala, is affected by play.
Repeated bouts of mating shrunk the size of motoneurons in the spinal cord.
taxi driver study
cab driver anterior hippocampus smaller and posterior bigger than regular people
-hippocampus associated with memory
expectaion of pain study
group one told it would really hurt when they put their hand in hot water
group two told it would only give them mild discomfort- showed dif brain activations
levels of analysis
range from social interaction down to the molecular level. Reductionism breaks a system down into its smaller parts, in order to understand it from the bottom up.
levels of analysis
social level, organ level, nueral systems level, brain region level, cellular level, synaptic level, molecular level
neurological, psychiatric disorder stat
Biological psychology can help to understand brain disorders and devise treatments.
One person in five suffers from some form of neurological or psychiatric disorder.
Clinical and laboratory approaches are both important in this research.
enlarged ventricles in brain- both the environment and your genes contribute to scitzophrenia
The study of biological bases of behaviour requires research on other species.
"Conservation of mechanism across phylogeny." -- rats and humans may be distant but have similarities
Serve as "stand-ins" for humans.
Provide important clues to disorders in humans.
Hot button issue.
what percent of the animals in the US are used for research?
five viewpoints that explore the biology of behaviour
1) describing behaviour: must be precise and reveal the essential features of behavour
2)studying evolution of behaviour : some aspects are continuous and some are species specific differences
3)development of behaviour and its biological charactersitics over lifetime
4) biological mechanisms of behaviour
5) studying applications of biological psych- eg. dysfunctions of human behaviour
The History of Research on the Brain and Behaviour Begins in Antiquity (far in the past, before middle ages)
ancient egyptians though the brain didnt play a huge role in society (they cared more about the heart which they preserved for the afterlife)
the brain was thrown away
do hebrew and chirstian texts mention brain?
Hebrew and Christian texts also do not mention the brain.
Aristotle: prominent Greek scientist, considered the brain
a "cooling mechanism"...a heat exchanger!
Herophilus: father of modern anatomy
dissected humans/animals—traced nerves, etc.
treated Gladiators with head wounds; detailed behavioural changes and made the connection that the brain was important.
Renaissance scientist Leonardo da Vinci
pioneered anatomical drawings, including the use of cross-sections
Anatomists emphasized the _____ surfaces of the brain.
Artists recognized the complexity of the brain, believing it was God's gift to mankind.
and they replicated the brain through hidden imagery in art
In Descartes' book (De Homnie) he:
Explained animal behaviour in terms of a machine.
Proposed the concept of spinal reflexes and their neural pathways.
Proposed the pineal gland as the junction between mind and body- structurally, the pineal gland is "singular" like consciousness.
an early account of reflexes
Sensory information produced tiny vibrations
that resulted in tiny valves. opening up in the brain
-"Animal spirits" leaked down tubes to the muscles.
-Muscles filled with fluid, causing them to "contract
-in reality motor neuron sends signal to spinal chord and reaction happens autmatically with no will
fearing opposition from the church... decartes withheld
publication of his book; published after his death in 1662.
Dualism is the idea put forth by Descartes that humans have a nonmaterial soul as well as a material body (bit of a cop out).
Not accepted by neuroscientists.
bumps on skull tell you about character
-looked at location of function
led to many myths lie we only used 10% of our brain power
Dr. wilder pendfield
-understood certain regions of the brain had deisngation for emotion, memory etc
-woman was having seizures and smelling burnt toast
-he was able to probe the part of her brain where the seizures were occuring and solve her problem
-he mapped the brain and provided detailed descrpition of cortex and how it related to behaviour
showed that language ability is restricted to a small area, based on a patient with damage in that region.
local damage caused inability to speak.
Scientists had long recognized that there was a relationship between ____ and intellectual ability.
____ invented the correlation coefficient to see if there was a relationship between head size and intelligence
Although Galton found no relationship, other 19th century scientists measured ____ as a better indicator of brain size
With the development and standardization of intelligence quotient (IQ) tests in the 20th century, scientists did find a correlation between ____and intelligence.
More recent techniques, using more direct measures of brain size, show a positive correlation between brain size and ____
A very small percentage of the variability in IQ _____ can be accounted for by differences in brain size.
about 10 %
Elephants have very large brains, but they aren't flying through wormholes!
Number of synapses matter; how
they are interconnected is important
Modern biological psychology arose in the 20th century.
Important studies were conducted on:
Learning and memory, conditioning, perception, and motivation.
D. O. Hebb described neuronal connections such as cell assemblies and Hebbian synapses. Nerves that fire together wire together!
Most scientists agree that consciousness is
the state of awareness of one's own existence and experience, is important and is connected to brain activity
We can study individuals that lose consciousness; _____also causes a loss of consciousness.
Consciousness allows us to do important things like ___ and _____
planning and reaching conclusions
The ___ parts of our brain are important for arousal, and ____ parts of the brain are responsible for current experience.
when presynaptic cell fires constant;y
post synaptic cell has higher activity
Neurons, or nerve cells:
are the most important part of the nervous system.
-100-150 billion of them; different phenotypes/functions.
-Specialized for chemical and electrical communication
Glial cells (plural- glia; "glue"):
provide support for neurons, regulate nerual communication, provide nutrition, important for damage in nervous system- they repair!; do so much more.
-100-150 billion; different phenotypes/functions.
-Do not produce electrical signals.
invented the "riazione nera"- black reaction product.
Results in the deposition of a dark reaction product in the dendrites, soma, and axon...basically outlines the entire neuron
-1st time we visualized the structure
Santiago Ramon y Cajal
Prodigious neuroscientist; suggested neurons were separate.
did elaborate drawings using Golgis technique
-often clashed with scientists in the states
Neuron Doctrine states that:
The neuron is the basic functional and structural unit of the brain.
Neurons are not continuous; Information is transmitted from cell to cell across synapses.
Neurons are made up of 3 parts: dendrite, soma, axon.
Information flows from dendrite, to soma, then down the axon.
input in neurons and output
from sensory apparatus or another cell through dendrites, output info is sent to next cell.
Techniques to VISUALIZE neurons: Golgi stains
fill the whole cell, including details, but only stain a small proportion of neurons. Fluorescent molecule injections give a similar result.
Techniques to VISUALIZE neurons: Nissl stains
outline all cell bodies because the dyes are attracted to RNA, which encircles the nucleus
Techniques to VISUALIZE neruons: Autoradiography
cells are manipulated into taking photographs of themselves
shows the distribution of radioactive chemicals in tissues.
Techniques to VISUALIZE neruons: Immunocytochemistry
can detect a protein in tissue. Brain slices are exposed to antibodies that are selective for a particular cellular protein of interest to the researchers. Antibodies attach to protein and chemcials make antibodies visible. the process reveals only those cells that were making the specific protein.
Immediate early genes (IEGs)
When neurons become more active, they tend to express immediate early genes. By using immunocytochemistry to label the IEG product, reserchers can identify brain regions that were active during particular behaviours performed by an animal before it was sacrificed
Techniques to VISUALIZE neurons: In situ hybridization
uses complementary radioactive probes to find neurons with a specific mRNA sequence.
Techniques to VISUALIZE neurons: Tracing Pathways in the Brain (tract tracing):
uses radioactive molecules or viruses taken up by the cell and then transported to the axon tips; virus then jumps the synapse to the next cell.
If it dies after jumping one synapse= direct connection
Techniques to VISUALIZE neurons: Retrograde labeling uses horseradish peroxidase (HRP)
it is taken up in the axon terminals and transported to the cell bodies, then visualized through chemical reactions.
Techniques to VISUALIZE neurons: CLARITY: Clear, Lipid-exchanged, Acrylamide-hybridized Rigid, Imaging/immunostaining compatible, Tissue hYdrogel
Turns the brain "clear" by embedding the brain into a gel and then removing the lipid layers.
Neurons are classified by shape, size, or function:
one axon, many dendrites—most common type
Neurons are classified by shape, size, or function: Bipolar neurons
one axon, one dendrite
Neurons are classified by shape, size, or function: unipolar neurons
a single extension branches in two directions, forming a receptive pole and an output zone (cell body in the centre)
stellate nerve in squid
can see neuron with the naked eye- highly used in research
Have more complex inputs and outputs; can handle more "information".
Cover greater distances.
Convey information more rapidly.
Motoneurons (motor neurons)
stimulate muscles or glands; degenerate in ALS- Amyotrophic lateral sclerosis, SBMA- spinal bulbar muscular atrophy
respond to environmental stimuli, such as light, odour, or touch; sensory neuropathy.
receive input from and send input to other neurons
The neuronal cell body and dendrites receive information across ___.
Dendrites have a branched arborization pattern to facilitate ____.
Information is transmitted from the
------ neuron to the ____ neuron.
Synapses have three components:
Presynaptic membrane—on the axon terminal of the presynaptic neuron.
Postsynaptic membrane—on the dendrite or cell body of the postsynaptic neuron.
Synaptic cleft—a gap that separates the membranes.
contain a neurotransmitter, a specialized chemical substance.
released in response to electrical activity in the axon; make their way to the post synaptic membrane via simple diffusion.
on postsynaptic membrane
-specialized proteins that "react" to a neurotransmitter; change their shape when a NT binds to the receptor.
are studded on the dendrites and increase surface area.
The property of neural plasticity in dendritic spines allows
their number and structure to be rapidly altered by experience.
Don't need to sign up to a company (e.g., Lumosity) to "change" your brain.
a cone-shaped area of the cell body that gives rise to the axon; contains action potential "generation zone".
a branch of an axon that also ends in terminals and innervates other cells.
the movement of materials within an axon; to or from the axon.
Slow transport (<8mm/day) or fast transport (200-400mm/day).
glial cells: Astrocyte
Glial cells support neuronal activity:
•Astrocytes—star-shaped cells with many processes that receive neuronal input and monitor activity.
•Form the "blood-brain barrier"; regulate flow of material into brain.
glial cells: Microglia
Migrate to site of injury, but usually present in the brain when inactivated
Also engulf cell debris
Is a glial cell that supports neural activity
•Microglial cells, or microglia—small cells that remove debris from injured cells; garbage collectors.
Myelination—the process in which glial cells wrap axons with a fatty sheath, myelin, to insulate and speed conduction.
Nodes of ranvier
Nodes of Ranvier—gaps between sections of myelin where the axon is exposed.
Multiple sclerosis—a demyelinating disease; possibly caused by an autoimmune disorder. Attacks myelin and it degenerates
Not fatal—suffers can expect a near normal life-span.
glial cells: Oligodendrocytes
Glial cells form myelin In brain and spinal chord-can be cancerous with rapid cell division
glial cells: Schwann cells
Schwann cells provide myelin to cells outside the brain and spinal cord.
Glial cells respond to injury by edema, or swelling, and are also susceptible to tumours
Glial cells can stop synaptic transmission by:
Entering synaptic cleft
Peripheral nervous system
The peripheral nervous system—all parts of the nervous system found outside the skull and spinal column
Central nervous system
The central nervous system (CNS) consists of the brain and spinal cord.
Features of the nervous system visible to the naked eye
PNS three components: spinal nerves
•Spinal nerves—also called somatic nerves connected to the spinal cord.
Peripheral nervous system
consists of nerves, (bundles of axons) and has three components:
PNS three components: cranial nerves
•Cranial nerves—connected to the brain.
PNS three components : autonomic nervous system
Autonomic nervous system—primarily controls glands and internal organs.
Cauda equina means
PNS consists of
PNS consists of nerves: axons bundled together.
3 main components: cranial nerves, spinal nerves, Autonomic Nervous System (ANS).
Cranial nerves—12 pairs; broken down into purely sensory, motoric, or a mix of both.
Enter at the base of the skull and do not join the spinal cord.
Sensory info to brain; motor info away from brain.
Cranial nerve 1:
Cranial nerve ll:
Criminal nerve lll:
Oculomotor: muscles that moves eye
Cranial nerve llll:
Muscles that move eye
Cranial nerve Vl
Abducens: muscle that moves eye
Cranial nerve V
Face sinuses teeth
Cranial nerve VII
Tongue, soft palate
Cranial nerve VIII
Inner ear, hearing and balance
Cranial nerve IX
Taste talking and other mouth sensations
Cranial nerve X
Information from internal organs
Cranial nerve XI
Cranial nerve XII
Spinal nerves or somatic nerves—31 pairs
Each spinal nerve is the fusion of two distinct branches, or roots:
•Dorsal (back) root—carries sensory information from the body to the spinal cord.
•Ventral (front) root—carries motor information from the spinal cord to the muscles to control movement.
How are spinal nerves named?
Spinal nerves are named for the segment of spinal cord they are connected to:
Lumbar (lower back)—5
Spinal nerve area cossix=
Spinal chord is surrounded by:
Vertebrae and meninges
Dorsal root ganglion sends:
Connections to periphery and spinal column. It gets sensory info
Grey matter is
White matter is
Axons In myelin sheath
Autonomic Nervous System (part of PNS): list three types of neurons
The Autonomic Nervous System spans the central and peripheral nervous systems
Groups of neurons, called autonomic ganglia, are located outside the CNS.
Preganglionic neurons run from the CNS to the autonomic ganglia.
Postganglionic neurons run from the autonomic ganglia to targets in the body
Autnonomic nervous system: Three major divisions
Sympathetic nervous system
Parasympathetic nervous system
Enteric nervous system
Sympathetic nervous system
Has preganglionic neurons only in the spinal cord—they innervate the sympathetic chain, which runs along each side of the spinal column
Sympathetic activation prepares the body for action.
Parasympathetic nervous system
Has preganglionic neurons that arise in the cranial nerves and the sacral spinal cord.
Parasympathetic activation is often in opposition to sympathetic activity.
Example: heart rate is slowed by parasympathetic activity, increased by sympathetic.
what NT does sympathetic neuron produce?
norepinephrine or noradrenaline to accelerate activity; "fight-or-flight" transmitter (actually a hormone released from the adrenals).
what NT does parasympathetic neuron produce?
Parasympathetic neurons produce acetylcholine; neurotransmitter. "rest and digest"
Enteric nervous system:
A local network of neurons that governs function of the gut.
Innervated by both sympathetic and parasympathetic divisions.
Central nervous system:
Consists of brain and spinal cord
The brain is dominated by two cerebral hemispheres; connected by white fibre tracts. (corpus callosum)
The cerebral cortex is the outermost layer of the cerebral hemispheres; the "bark".
The brain surface has two types of areas. What are they?
A gyrus (plural- gyri) is a ridged or raised portion of the convoluted brain surface.
A sulcus (plural- sulci) is a furrow of the convoluted brain surface.
important for motor skills
post central gyrus
important for sensory info
executive functioning, planning
severing corpus callosum
may stop seizures, also causes split brain and some people report that their left hand no longer belongs to them and starts doing unwanted tasks like unbottoning their shirt with left hand when they are trying to button it with right
Potential cause of diseases- vit B deficiency
Wernickle-Korsakoff Syndrome :(
the mamillary body is very susceptible to vit. B dficiency and people can get a memory disorder because of a lack of it. It causes degeneration of the mamillary body and memory problems
what is the name of disease associated with Vit. B deficiency?
Wernickle- Korsakoff Syndrome
bisects the brain into right and left halves
divides the brain into front (anterior) and back (posterior) regions
divides the brain into an upper and lower part
towards the middle
towards the side
near the centre
toward the periphery
The cerebral hemispheres include four lobes:
Frontal—most anterior region
Parietal—lies between the frontal and occipital lobes
Occipital—posterior region, visual processing
Temporal—lateral region, auditory processing
Boundaries between lobes
Sylvian fissure (lateral sulcus)—boundary of the temporal lobe
Central sulcus—divides the frontal lobe from the parietal lobe
a strip of cortex behind the central cortex, important for touch
in the frontal lobe, important for motor control
Corpus callosum (is a gyrus)
a bundle of axons that connects the two cerebral hemispheres
Two colours of brain tissue and what they signify
White matter—consists mostly of axons with white myelin sheaths
Gray matter—contains more cell bodies and dendrites, which lack myelin
Within the CNS: what is another use of the word nucleus?
a collection of neurons
Within the CNS:
what is a tract?
a bundle of axons
In PNS neurons form ganglia and bundles of of axons are nerves.. what is the exception
basal ganglia in brain
shows nuclues through stain in rat brain- large in males and small in females. IT is important in regulating sex behaviour- testosterone is important to its appearance
is the brain bilaterally symetrical?
The brain, with the exception of a few structures, is bilaterally symmetrical.
In general, each side of the brain controls and receives information from the opposite (contralateral) side.
Neocortex, or isocortex,more simply called cortex, has six distinct layers. What is its function and How are the layers distinguished?
Complex cognitive processing.
Cortical layers are distinguished by:
Type of neuron.
Pattern of dendrites or axons.
layer l has few cell bodies, layer V and VI have many cell bodies
three layers, or is unlayered; limbic system.
are the most prominent neurons in cerebral cortex.
Pyramid-shaped cell body in layer III or V.
Apical dendrite extends vertically to outermost cortex.
Basal dendrites spread horizontally from cell body.
Neurons in the cortex are organized into cortical columns.
Each column is perpendicular to the cortical layers and serves as a unit to process information.
Cortical regions communicate with one another via tracts of axons.
Cortical columns operate as a unit
Human Connectome Project
Mapping of the human connectome (neural connections in the brain) offers a unique opportunity to understand the complete details of neural connectivity (Sporns et al., 2005, Wedeen et al., 2008, Hagmann et al., 2007). The Human Connectome Project (HCP) is a project to construct a map of the complete structural and functional neural connections within and across individuals. The HCP represents the first large-scale attempt to collect and share data of a scope and detail sufficient to begin the process of addressing deeply fundamental questions about human connectional anatomy and variation
Within the cerebral hemispheres: 4 nucilei (group of neurons) in basal ganglia important for motor control
The basal ganglia, important in motor control, include four nuclei:
The caudate nucleus, the putamen, and the globus pallidus under the cerebral cortex.
The substantia nigra, in the midbrain-- degeneration associated with parkinsons disease
The Limbic system includes structures important for learning and memory such as?
Amygdala—"almond" emotional regulation and perception of odour.
Hippocampus and fornix—some forms of learning and memory.
Cingulate gyrus—attention. Lights up when people are in fear
Olfactory bulb—sense of smell.
group of forebrain nuclei (collection of neurons in CNS) found deep within cerebral hemishperes
activity in cingulate gyrus- if you destroy cingulate gyrus you will have absolutely no fear
More of the limbic system in addition to amygdala, hippocampus and fornix, gingulate gyrus, and olfactory bulb:
The thalamus—a cluster of nuclei that relay sensory information.
The hypothalamus—contains nuclei with many functions—also controls the pituitary; the "4 F's". e.g. fleeing, fighting, feeding, fornicating
Mamillary bodies— recollective memory; degenerate in alcoholics; Wernicke-Korsakoff syndrome (thiamine deficiency).
Midbrain sensory systems:
Bumps at the top of the brainstem.
Superior colliculi—process visual information.
Inferior colliculi—process auditory information.
Together, these are known as the tectum.
Midbrain motor systems continued:
Substantia nigra—part of the basal ganglia. It is essential for dopamine trnasmission- if this function stops working it results in parkinsons, L.Dopa is the treatment for parkinsons and is a precursor to dopamine. You lose 80% of cells in substancia Nigra in parkinsons
Red nucleus—communicates with motoneurons in the spinal cord; part of a circuit needed for conditioning ("eye blink").
Other systems in the midbrain:
Reticular formation—involved with sleep and arousal, temperature control, and motor control.
The midbrain also gives rise to several cranial nerves. IF a person is in a coma, their reticular formation is impaired
Cerebellum—involved in motor coordination and learning. IT provides minor connections between intended actions and actual outcomes. consists of three layers:
Granule cell layer—cells send axons to form parallel fibers in the outermost, or molecular, layer.
Purkinje cell layer—the middle layer, its cells form a single row.
The pons is attached to the cerebellum and contains motor and sensory nuclei and gives rise to cranial nerves.
The medulla contains cranial nerve nuclei and marks the transition from brain to spinal cord; breathing centre.
Edinger- Westphal nucleus
if a person has been badly injured in a car accident, paramedics will ofter flash a flashlight in their eye because they are looking to see their pupil. if there is no pupil there is likel damage to the edinger westphal nucleus in brain stem
is someone didnt speak well in childhood and it took them a long time to be able to walk- what part of their brain is likely missing?
The brain and spinal cord are surrounded by three protective membranes, the meninges: Called?
Dura mater—tough outermost sheet.
Pia mater—delicate innermost layer.
Arachnoid membrane—lies between the other two, is filled with cerebrospinal fluid (CSF).
The ventricular system is a series of chambers filled with CSF.
what are the CSF main functions?
Acts as a shock absorber.
Provides an exchange medium between blood and brain.
CSF is also very important for waste management- protective function to the brain
why is cerebral spinal fluid so important?
-protects the brain from injury and maintains buyouncy
--prevents brain from spreading around if damaged
-coup- brain damage, countercoup is rebound
The lateral ventricle in each hemisphere extends into all four lobes and is lined with the choroid plexus, a membrane that produces CSF.
CSF flows into the third ventricle at the midline, then into the _____
fourth ventricle where it exits to circulate over the brain and spinal cord.
The carotid arteries are the major arteries to the brain.
The internal carotid artery branches into
anterior and middle cerebral arteries.
Vertebral arteries enter the skull and form the
basilar artery, which gives rise to the posterior cerebral arteries.
The circle of Willis
is a structure formed by the major cerebral arteries.
Capillaries brach off to feed all cells in the brain; exposure to substances must be limited.
The blood-brain barrier
restricts passage of large molecules into brain.
is caused by the rupture or blockage of blood vessels, leading to insufficient blood supply.
-people tend to lose function in Broca and Wernickle's area after stroke
formation of blood clots—> may migrate; treated with Warfarin (kills rats! Its an anticlotting medication)
what can pass through the blood brain barrier unimpeded?
alcohol- to some extent
-steroids (anabolic steroids)- can result in cell death in hippocampus
X-ray of head with dye present in cerebral blood vessels.
Can reveal acclusion
Computerized axial tomography (CAT or CT)
maps tissue density
a measure of X-ray absorption at several positions around the head, maps tissue density.
-dense objects absorb the X-rays.
Magnetic resonance imaging (MRI)
gives higher resolution images than CT, maps the density of the brain with high detail and no exposure to potentially harmful X rays like in CT. 1) patients head placed into center of powerful circular magnet- causes all protons in brain tissue to line up in parallel 2) protons knocked over by strong radio waves, when pulse turned off the protons relax backk to original configuration, emitting radio waves as they go, The emitted radio frequency vaires with density of various tissues... lastly powerful computer uses density based info to generate detailed cross section map of brain
Positron emission tomography (PET)
gives images of brain activity:
Uses radioactive chemicals injected into the bloodstream and maps their destination by the radioactive emissions.
Identifies which brain regions contribute to specific functions.
isolating specific brain activity- must have baseline
brain activity stimulus minus baseline= activity in visual cortex
Functional MRI (fMRI)
detects small changes in brain metabolism, such as oxygen use, in active brain areas.
The amount of oxygen available is measured indirectly, on the basis of blood flow or the state of hemoglobin in blood (called the blood-oxygen-level-dependent, or BOLD, signal).
fMRI can show how networks of brain structures collaborate.
false positives with fMRI
tested a dead trout and brain activation was seen
Diffusion Tensor Imaging (DTI)
uses the diffusion of water molecules within tissue to determine the orientation of fibre tracts within the brain.
DTI provides a noninvasive method to map the fine axonal connections between different regions of the living human brain.
Transcranial magnetic stimulation (TMS)
strong focal magnetic currents used to briefly stimulate the cortex of alert normal subjects. Enables experimenters to activate discrete areas of the cortex through process of elctromagnetic induction. The regions stimulated and resulting behaviours can be tracked and mapped. MAYO clinic uses TMS to treat individuals with depression and schitzophrenia- reduces voices in their head
Imaging can overcome the limitations of other methods of assessment and complement traditional studies of brain :
lesions (regions of damage).
One question that can be addressed is the state of consciousness of people in comas.
Brain areas in such people can show activation when prompted.
People with brain damage sometimes also have fewer sulci
like fMRI, have high spatial resolution (provide a lot of structural detail) but are...
relatively slow in making images.
Thus, these techniques have low temporal resolution and do not track dynamic changes in brain activity well.
Some techniques, like MEG and EEG, have high temporal resolution but low spatial resolution.
Researchers must weight these trade-offs when designing experiments.
is the study of the life processes within neurons that use electrical and chemical signals.
Resting membrane potential
is a difference in the electrical charge inside compared to the outside of a neuron.
-inside neuron is more negative due to the movement of ions, selective permeability of membrane, and an ion pump
is a rapid electrical signal that travels along the axon of a neuron.
is a chemical messenger between neurons.
Resting membrane potential-what is it due to?:
when a neuron is quiescent (quiet- never 100%), the inside charge is different than the outside.
Due to the movement of ions, selective permeability of the neuronal membrane, and an ion pump.
how do we know the difference of electrical charge in a neuron?
-compare baseline- reference electrode and recording electrode-- experiments done with large squid axon
resting membrane potential number
about -60 mV--> shows the negative polarity of the cell's interior.
Intracellular proteins have a net negative charge- contribute little to negativity
inserted into a resting cell shows that it is more negative than the extracellular fluid
Ions and anions and cations
electrically charged molecules; due to an imbalance in the number of electrons versus protons.
Anions are negatively charged and cations are positively charged.
Ions are dissolved in intracellular fluid, separated from the extracellular fluid by the _____
The cell membrane is a _____, with two layers of lipid molecules.
hydrophobic tail- water hater
hydrophillic head-water lover
-molecules with charge cannot pass straight through membrane, molecules that arent charged can slip through
the lipid bilyaer does what?
Selectively permeable; separates intra- and extracellular environment.
are proteins that span the membrane and allow ions to pass
Gated ion channels
open and close in response to voltage changes, chemicals, or mechanical action.
Ions important for the generation of the resting membrane potential. which ones?
1. K+ (kalium): a.k.a., Potassium (first isolated from potash).
2. Na+ (natrium): a.k.a, Sodium.
1. Ca++: a.k.a., Calcium.
2. Cl-: a.k.a., Chloride.
Some channels are open all the time and allow only ______) to cross via diffusion.
potassium ions (K+)
The neuron shows selective permeability to (K+)—it can enter or leave the cell freely.
Resting potential—balance between 2 forces that drive K+ ions in and out of the cell.
Two opposing forces drive ion movement:
Diffusion causes ions to flow from areas of high to low concentration, along their concentration gradient.
Electrostatic pressure causes ions to flow towards oppositely charged areas; "opposites attract".
what mechanism do neurons use to maintain the resting potential?
sodium potassium pump
-Requires the production of energy to run the Na+/K+ pump...30% of metabolism is utilized!
-It pumps three sodium ions (Na+) out for every two K+ ions pumped in; concentration is thus established.
lipid bilyaer of membrane acts like:
insulator- electrostatic pressure drawing ions closer to eachother
-they stay lined up in this fashion without pushing away like charged ions (see diagram in notes)
adenosine tri phosphate
inorganic phosphate- transfers its phosphate releasing energy
do the negatively charged proteins in the cell want to get out to where its more positive?
yes outside of cell
what is the result of the sodium potassium pump?
more positive charges leaving the cell than entering
at rest where do the K ions move?
At rest, K+ ions move into the negative interior of the cell because of electrostatic pressure.
-As K+ ions build up inside the cell, they also diffuse out through the membrane, down the concentration gradient. (To outside of cell)
-Constant flow until the two forces balance out.
can sodium permeate membrane as easily as K?
-it would make the cell more positive, sodium leakage actually keeps the resting potential at average of -60mV
when does potassium reach equilibrium?
K+ reaches equilibrium when the movement out is balanced by the movement in.
This corresponds to the resting membrane potential of about -60 mV (values may range between -50 and -80 mV, it depends upon the cell type).
- the movement of K+ is what drives the resting membrane potential.
what DRIVES the resting potential
movement of K
poised for action potential
The Nernst equation predicts the voltage needed to counterbalance the diffusion force pushing an ion across a membrane.
This prediction is the resting membrane potential for that ion
where is chloride highly concentrated?
on outside of cell, wants to flow down concentration gradient into cell--> hyperpolarization
what is the language of the neuron?
Resting membrane potential for... what?
action potentials- necessary first step in neuronal communication.
The neuron is ready—> just needs the proper signal.
-they are constantly active not just sitting latently awaiting action potential
Action potentials are:
are brief but large changes (reversals, actually) in membrane potential.
where do action potentials originate?
They originate in the axon hillock and are propagated along the axon; high concentration of Na+ channels.
-Patterns of action potentials carry information to postsynaptic targets.
decreases chance of firing action potential- becoming more negative. farther away from 0
less negative, higher chance for action potential
is an increase in membrane potential—the interior of the membrane becomes even more negative, relative to the outside.
-Moves from -60mV to -80mV...no chance for an action potential to fire.
is a decrease in membrane potential—the interior of the cell becomes less negative.
A hyperpolarizing stimulus produces
an immediate response that passively follows the stimulus; opening of a Cl- channel.
-The greater the stimulus the greater the response—the change in potential is called a graded response.
as the potential spreads across the membrane, it diminishes as it moves away from the point of stimulation.
are changes in membrane potential after action potentials.
-happen because you dont want your cells to continuously fire
A depolarizing stimulus produces :
local, graded responses.
-If the membrane reaches the threshold (about -40 mV), it triggers an action potential.
The membrane potential reverses and the inside of the cell becomes positive
All-or-none property of action potentials and afterpotentials
the neuron fires at full amplitude or not at all. This does not reflect increased stimulus strength.
-Action potentials increase in frequency with increased stimulus strength; frequency of APs "encode" information.Afterpotentials are changes in membrane potential after action potentials.
depolarizing in numbers
-40mV to +40 mV
what are action potentials produced by?
Action potentials are produced by the movement of Na+ ions into the cell; high conc. at axon hillock.
- At the peak of an action potential, the concentration gradient pushing Na+ ions in equals the positive charge driving them out.
Membrane shifts briefly from a resting state to an active state and back.
Voltage-gated Na+ channels open in response to :
the initial depolarization.
-More voltage-gated channels open and more Na+ ions enter.
This continues until the membrane potential reaches the Na+ equilibrium potential of +40 mV.
As the inside of the cell becomes more positive, voltage-gated K+ channels
OPEN and K+ moves out (is pushed out) and the resting potential is restored.
proteins exist in certain shape, (conformation) so this is a change from one state to another
which gate is stronger? NA or K
too much K flows out
without the refractory phase in the cell what would happen?
cell would hyperexcite itself
time when only some stimuli can produce an action potential.
Absolute refractory phase
time when no action potentials are produced.
Relative refractory phase
time when only strong stimulation can produce an action potential.
apamin; modifies AHP, making cells hyper excitable.
-Can deal with a small amount of stings, but large amounts cause seizures, potentially death.
Ion channels are very specific in their function: how?
K+ channels are lined with oxygen atoms that mimic water molecules.
K+ ions pass through this selectivity filter more easily than Na+; Na+ prevented from passing through pore
Golden poison frog; "batrachos" = frog
BTX forces Na+ channels to stay open; longer action potential. Hyperstimulating cell!
it is lipophyllic- Can slip through membranes! Including into the brain
Uncontrollable convulsions, heart failure, suffocation in under 10 mins.
-in lab, their poison capability is gone-- suggests it originates from something they're eating
pufferfish ovaries, liver, lungs.
In Asian cultures called "fugu" -- eat pufferfish that has been prepared by chef who knows how to cut around toxic parts
-TTX blocks Na+ channels; no action potentials.
-potential use? Anethesia!
dinoflagelletes; algal species produce them; typically harmless.
-eaten by clams, who concentrate the STS, humans eat them and then get poisoned!
Red Tide: algal bloom; don't eat the shellfish.
Blocks Na+ channels.
Typical in California and Pacific Northwest.
Chinese Red Headed Scorpion
Venom is a Na+ channel blocker.
9 different "flavours"; venom blocks pain transmitting channel (Nav1.7).
-Channelopathy—genetic abnormality of ion channels; Nav1.7 mutations in humans. They cannot feel pain!
-pain is necessary for survival
receptors in skin that detect pain use what channel to send pain signal?
(Nav1.7).-- Na channel
are action potentials continuous or regenerated?
-Action potentials are regenerated along the axon—each adjacent section is depolarized by an action potential, creating a new one.
—the speed of propagation of action potentials—varies with diameter.
-large calliber of axon is advantageous-- its quicker!
when sodium flows inside cell during action potential and the Na channels close what happens?
inside becomes positive compared to negative outside
axons are filled with ____
microtubules that Na can bump into on its way to the end of the axon. In smaller axons Ma ions can travel very far before they bump into something
-lrg axons = faster!
what helps speed up the process in small axons?
mylenization- increases capicitance and increases velocity. Acts as an insulator
Nodes of Ranvier
small gaps in the insulating myelin sheath.
the axon potential travels inside the axon and jumps from node to node.
estimate of unmylenated axons in saltatory conduction per 1 m
100 ms/ meter
estimate of mylenated axons and saltatory conduction per 1m
how do synapses cause local, graded potentials in the post synaptic membrane?
Electrical signal is converted into a chemical signal (i.e., a neurotransmitter).
One of the ways a neuron talks to another neuron.
Besides chemical synapses, there are electrical synapses, or gap junctions.
electrical synapses/ gap junctions
in these regions, the axon potential can jump directly to the postsynaptic region without first being transformed into a chemical signal.
Ions flow directly through large channels into adjacent cells, with no time delay.
Much faster transmission of signals from one cell to the next.
-often found with motor neurons
neurotransmitters can be ___ or ____
excitatory or inhibatory
are brief changes in the resting potential when NT binds to receptor.
Excitatory postsynaptic potential (EPSP)
produces a small local depolarization, pushing the cell closer to threshold; Na+ ions.
- If large enough (or if enough come together at once), may cause generation of AP.
Inhibitory postsynaptic potential (IPSP)
produces a small hyperpolarization, pushing the cell further away from threshold
- IPSPs result from chloride ions (Cl−) entering the cell, making the inside more negative.
enough depolarization at the same time causes ___
the Na channels to open at the axon hillock
what do neurons perform to integrate synaptic inputs?
IPSPs and EPSPs are summed.
A postsynaptic neuron will fire an action potential if a depolarization that exceeds threshold reaches its axon hillock.
Net summation of PSP's is positive (to or beyond threshold)= AP fired.
is the summing of potentials that come from different parts of the cell.
If the overall sum—of EPSPs and IPSPs—can depolarize the cell at the axon hillock, an action potential will occur.
is the summing of potentials that arrive at the axon hillock at different times.
The closer together in time that they arrive, the greater the summation and possibility of an action potential.
occurs naturally within the body:
substances that the brain/body produces; e.g., neurotransmitter, hormone, neuromodulator, etc.
Affect brain and behaviour.
introduced from outside the body; substances can also affect brain and behaviour; mimic endogenous substances.
Neurotransmitters affect neuronal functioning. How?
Induce EPSPs and IPSPs in post synaptic neuron.
"Lock and Key" analogy.
NT is a key that fits into a specific lock (protein) on post synaptic cell-- effect is EPSP or IPSP
Criteria for neurotransmitters—chemicals released onto target cells:
-Substance exists in presynaptic axon terminals.
-Is synthesized in presynaptic cells.
-Is released when action potentials reach axon terminals.
-Receptors for the substance exist on postsynaptic membrane.
- When applied, substance produces changes in postsynaptic cells.
- Blocking substance release prevents changes in postsynaptic cell.
Neurotransmitters affect targets by acting on receptors— which are?
protein molecules in the postsynaptic membrane.
are fast—open an ion channel when the transmitter molecule binds
are slow—when activated they alter chemical reactions in the cell, such as a G protein system, to open an ion channel.
the same neurotransmitter may bind to a variety of subtypes ("flavours"), which trigger different responses.
what do drug companies target for creating compounds?
Drug companies target receptor subtypes for development of compounds with particular effects.
is a substance that binds to a receptor and has one of three effects:
initiates the normal effects of the receptor.
blocks the receptor from being activated by other ligands.
what are antagonists usually?
the effects of different isoforms and drugs targeted to these isoforms: antidepressants
side effects of antidepressants due to these many isofroms, e.g. dont want to have sex, suicide, loss of energy
when taking a prozac... for example...what is the process that happens?
chloride channel=open as it always is- hyperpolarization. barbiturates and benzodiapines bind to this channel, GABA binds after it sees these two to make the pore even larger and cloride moves into the cell more.
-this is agonist activation
bind to the same part of receptor molecule as endogenous ligand.
bind to modulatory sites that are not part of the receptor complex that normally binds the transmitter.
Prevents protein from completing its function
it is bound to site at secondary binding side
ex) car with boot on it
or co-release—occurs when nerve cells contain more than one type of neurotransmitter.
They can contain excitatory and inhibitory NT at the same time
mapped by the enzymes involved in its synthesis.
-we follow the enzymes because ACH itself is dispersed all over the brain
Cholinergic nerve cell bodies and projections contain:
where do we see widespread loss of cholinergice fibres?
Alzheimer's disease; may be crucial for learning and memory.
Acetylcholinesterase inhibitors (AchEI)
e.g., Aricept; approved for treatment of Alzheimer's; increases levels of Ach in brain.
cholinergic antagonist; interferes with learning and memory.
Acts as memory blocker
breaks down acetylcholine and shuts down its transmission; Sarin gas inhibits AchE = increased excitability (esp. at NMJ's). Prevents ability of ACH to shut off-- muslces twitch and flex and there is overstimulation. Massive excitation!
what region of brain is responsible for ACH production?
The sequence of synaptic neurotransmission:
1) Action potential travels down the axon to the axon terminal.
2) Voltage-gated calcium channels open and calcium ions (Ca2+) enter.
3) Synaptic vesicles fuse with membrane and release transmitter into the cleft.
4)Transmitters cross the cleft and bind to postsynaptic receptors and cause an EPSP or IPSP.
5)EPSPs or IPSPs spread toward the postsynaptic axon hillock.
6) Transmitter is inactivated (by enzymatic degradation) or removed (by transporters for reuptake and recycling)—action is brief.
7)Transmitter may activate presynaptic autoreceptors, decreasing release.
when does switch from electric to chemical change occur during cell communication?
-when the calcium channels open, which allows vessicles full of NT to bind with presynaptic membrane
by design Neurotransmission is ____
Monoaminoxidase degrades ___
shape that vessicles produce:
A synapse that uses acetylcholine (ACh) has ligand-binding sites for ACh in the :
receptor molecules; portion of protein sticks out into cleft.
ACh can be excitatory, and open channels for Na+ and K+, or inhibitory, and open channels for Cl−.
Muscarinic ACh receptors:
found in the brain; also found on organs innervated by the parasympathetic division of the autonomic system.
These receptors played a role in the discovery of neurotransmitters in a famous experiment conducted by Otto Loewi (which helped him win the Nobel Prize in 1936).
autoreceptors do what?
detect how much NT is being duffused into synaptic gap, tell presynaptic cell to stop letting out NT
dreamt about nuerotransmission and ACH. 1st NT to be demonstrated to involve physiological process. He had second dream about neurotransmission and went straight to lab: couple hearts bathed in ion solution (fluid) and attached to eachother via a tube. Flow of liquid can be turned on/off. Looking to see whether vagus nerve slowed heart rate via electrical/ chemical signal. If tube stays closed- heart ontop slows and heart on bottom continues beating normally. Now pump opened and both hearts slow down- shows its chemical! ACH!
is there a static number of receptors? on post synaptic membrane
no! Receptors in post synaptic cell can be brought into soma for degredation
Otto Loewi experiment revisited
-There is no pumping of fluid between the two chambers and no stimulation of the vagus nerve. The hearts will continue beating for several hours under these conditions.
-Vagus nerve to heart A is stimulated but the pump is not on, so no fluid is circulated to heart B.
Result: Vagus stimulation slows heart A, but heart B remains unchanged.
-Vagus nerve to heart A is stimulated and the pump is circulating fluid from bath A to bath B.
Result: Vagus stimulation slows heart A, and heart B slows down as well.
Structure of the nicotinic ACh receptor determined—> led to?
led to the elucidation of the structure of receptors for other neurotransmitters (GABAa, glycine, glutamate).
-Similarities in receptor molecule structure suggests they belong to the same protein family and have a common evolutionary origin.
can the number of receptors in cell vary in adulthood?
The number of receptors in cells can vary daily in adulthood—also during development or with drug use.
is an increase in the number of receptors,
is a decrease in number of receptors
Various stimuli can cause up or down regulation-
e.g. drug abuse
Transmitter action is brief and termination can occur in two ways: degredation
Degradation- the rapid breakdown and inactivation of transmitter by an enzyme.
Example: Dopamine (DA)- synthesized from L-DOPA; released into cleft—> taken back up or degraded by MAO or catechol-O-methyl transferase (COMT).
Transmitter action is brief and termination can occur in two ways: reuptake
2. Reuptake—transmitter is taken up into the presynaptic cell.
Transporters are special presynaptic receptors involved in reuptake.
Some NTs bind to autoreceptors that inform the presynaptic cell about the net concentration of neurotransmitter in the cleft.
Too much, receptor decreases concentration by brining NT into cell = termination of signalling.
Types of synapses:
Axo-dendritic—axon terminal synapses on a dendrite.
Axo-somatic—axon terminal synapses on the cell body (soma).
Axo-axonic—between two axons.
Dendro-dendritic—between two dendrites.
axo axonic and dendrodenritic syanpses are____ common
dendrodendric usually have inc. speed of transmission
Types of synapses:
uses gas (such as carbon monoxide or nitric oxide) or other neurotransmitters (anandamide) to signal to presynaptic cell; may increase or decrease NT release.
A neural chain is:
a simple series of neurons; like circuits in a circuit board
The knee jerk reflex is :
is a circuit for the stretch reflex, consisting of:
The knee jerk reflex is extremely fast because:
Axons are myelinated and large.
Sensory cells synapse directly onto motoneurons.
Uses fast, ionotropic synapses.
what activates stretch receptor in knee jerk reflex?
deformation of mucle-- leads to glutamate release. change in shape of stretch receptor- depolarization and action potential!
The visual system is a circuit with other features:
Convergence—many cells send signals to one cell.
Divergence—one cell send signals to many cells.
Units are arranged in parallel, and have lateral interaction across units.
does brain take part in knee jerk reflex?
endogenous NT that is like THC and binds to CB! and shuts down calcium signalling- shuts down neurontransmission
pattern seperation is a result of ____ happening at dendate gyrus
divergence (e.g. noting that grass is soft and spiky and smells) and CA3 completes the pattern (processes and incorporates info) and sends it to CA1
is NS well organized?
not really.. completely different cells with different functions side by side
uses genetic tools to insert light-sensitive ion channels into neurons; genes for encoding channels are introduced into genome of host organism.
Stimulating the brain with light, delivered by fiber-optic cables, can excite or inhibit those targeted neurons.
Some algae and bacteria produce light-sensitive proteins called
opsins, which resemble the mammalian opsins found in light-receptor cells in our eye.
Channelrhodopsin responds to
blue light by allowing Na+ ions to enter the cell, depolarizing it = turn cells on.
Halorhodopsin responds to
yellow light by allowing Cl- ions into the cell, hyperpolarizing it = turn cells off.
Ventral Tegmental Area (VTA) sends Dopamine to
to Nucleus Accumbens (NAcc)
use light sensitive channels to turn cells
Tail suspension test- measure
of behavioural despair.
rat with no depressive symptoms will try to bite hand but rat with behavioural despair may try once but then gives up (VTA off)
Lack of sucrose preference- indicator of anhedonia.
animals with no depressive behaviour like taste of water with sucrose.
depressive animals dont care
-indicator of anhedonia-- dont do things that used to make you happy
Two types of ACh receptors:
most are ionotropic and excitatory
Example: muscles use nicotinic ACh receptors—paralysis can be induced with an antagonist, such as curare--> comes from plants in South America and hunter gatherer societies posion arrows with curare which are used to hunt small prey and it paralyzes them. Doesn't posion person who eats it.
Two types of ACh receptors:
metabotropic and can be excitatory or inhibitory.
Muscarinic ACh receptors can be blocked by atropine or scopolamine to produces changes in cognition.
Atropine is antidote for sarin.
Atropine blocks effect of sarin gas, comes from plant called Atropa Belladonna
Women used to put Atropine in their eyes bc large eyes were seen as attractive
Two main classes of monoamine neurotransmitters: Catecholamines
dopamine, epinephrine, norepinephrine; derived from amino acid, tyrosine found in BBQ foods and cheese
Two main classes of monoamine neurotransmitters:
melatonin, serotonin; derived from amino acid, tryptophan.
Found in chicken, turkey, salmon. Body can only handle a certain amount of amino acid- myth of turkey making you sleepy isnt true
Dopamine (DA) is found in neurons in: the mesostriatal pathway—originates in the midbrain, specifically the substantia nigra and innervates the striatum.
This pathway is important in motor control and neuronal loss is a cause of Parkinson's disease.
** dopamine is also released in aversive condition-- it signals salience- vividness!
The mesolimbocortical DA pathway:
The mesolimbocortical DA pathway originates in the midbrain—in the ventral tegmental area (VTA)—and projects to the limbic system and cortex.
DA in this pathway is involved in reward, reinforcement and learning; abnormalities are associated with schizophrenia.
Norepinephrine (NE) is released in three brainstem regions:
Locus coeruleus (pons)
Lateral tegmental system (midbrain)
Dorsal medullary group
NE is also known as noradrenaline—cells producing it are noradrenergic
Cell bodies for NE are found in:
cell bodies for seratonin are found in:
Noradrenergic fibers from the locus coeruleus project broadly... To where?
The CNS has four subtypes of NE receptors—all metabotropic.
The NE systems modulate processes including mood, arousal, and sexual behaviour.
Serotonin (5-hydroxytryptamine, 5-HT) cell bodies are mainly found in:
the raphe nuclei, and their serotonergic fibers project widely.
Serotonin is implicated in:
sleep, mood, sexual behaviour, and anxiety.
Antidepressants such as Prozac increase:
5-HT activity, with effects depending on which receptor subtype is affected...there are 19 subtypes...!
19 subtypes of receptors for seratonin: What are they all involved in?
active in antidepressant drugs
is glutamate excitatory/ inhibitory?
excitatory! **for exam know at least one glutamatergic receptors and that they are ionotropic
Amino acid transmitters: Glutamate and asparate
Glutamate and aspartate—excitatory.
Glutamatergic transmission uses AMPA, kainate, and NMDA receptors; ionotropic receptors.
Glutamate also acts on :
mGluRs—slower metabotropic receptors.
neural injury such as stroke may cause excess release of glutamate, which is toxic to neurons.
what is involved in the uptake of glutamate from the synapses?
Astrocytes are involved in the uptake of glutamate from the synapses.
Amino acid transmitters: Gamma-aminobutyric acid (GABA) and glycine
Gamma-aminobutyric acid (GABA) and glycine—inhibitory (in adulthood).
GABA receptors come in different flavours:
different flavours of GABA receptors: GABA a
GABAA—ionotropic, producing fast, inhibitory effects; Cl- channel. Decreases potential that action potential occurs.
different flavours of GABA receptors: GABAB
metabotropic, slow inhibitory effects; linked to g-proteins and K+ channels.
different flavours of GABA receptors: GABAC
ionotropic with a chloride channel.
GABA agonists, like Valium (diazepam) are:
potent tranquilizers; put the "brakes" on; bind to GABA receptor and increase pore size.
Blockade of GABA channels can produce seizures.
Peptides act as neurotransmitters at some synapses, or as hormones:
Opioid peptides mimic opiate drugs such as morphine; met-enkaphalin, B-endorphin, leu-enkaphalin, dynorphin...don't tell your mom.
Peptides in gut, spinal cord, or brain: Substance P, CCK, neuropeptide Y, etc.
Pituitary hormones: oxytocin, vasopressin.
The gas nitric oxide (NO) differs from other neurotransmitters:
It's produced in locations other than axon terminals—mainly in dendrites and diffuses as soon as it is produced, rather than released
It diffuses into the target cell and stimulates production of second messengers.
It serves as a retrograde transmitter by diffusing back into the presynaptic neuron
Many drugs are ligands that:
act upon specific receptor molecules.
Drugs may target one or a few receptor subtypes.
Because receptor subtypes have different localizations and functions, drug actions can have widely varying effects.
prescription medications or over the counter medications; "a medicine used in the treatment of disease".
e.g., marijuana, MDMA, etc; "molecular changes that lead to alterations in physiological or psychological functioning".
what causes difference between illegal drug and non-illegal drug?
coffee is a drug because it changes your physiology, difference between drugs and drugs of abuse is government regulation
what is The binding affinity (or "affinity")?
The binding affinity (or "affinity") is the degree of chemical attraction between a ligand and a receptor.
Drugs mimic endogenous ligands (neurotransmitters, steroids, etc).
Example of drug mimicking endogenous ligand:
People take cathecoline because of feelings of reward. It binds to dopamine receptors and many others. It is used in bath salts! High potential for abuse.
Binding affinity assay... aka do you like me?
Put recpetor and particular drug in to a solution and shake it up with some added radioactivity
low affinity drug: sometimes found bound to receptor
Higher affinity drug: More often found bound to receptor
-can also watch two in competition
The efficacy (or "intrinsic activity") is
the ability of a bound ligand to activate (change its conformation) the receptor...which is what it is intended to do.
Agonists have high efficacy vs antagonists which have ____
Partial agonists produce
a medium response regardless of dose.
what defines drug action?
Combo of affinity and efficacy that defines drug action.
Are NT weak in terms of affinity for our recpetors?
Yes! so they dont have a prolonged effect
A dose-response curve (DRC) is:
a graph of the relationship between drug doses and the effects.
The DRC is a tool to understand pharmacodynamics—the functional relationship between drugs and their targets
the functional relationship between drugs and their targets-- what drug does to body
Dose response curve:
X axis is dose- y axis is response from 0% to 100%
half max of response were interested in measuring- pharmacologically effective for 50% of the population exposed to the drug
what is the typical shape of does response curve?
Like an S- 0 dose= 0 effect, Does increases as effect increases but plateaus because all the receptors are occupied. Only effective to certain point!
How do you measure potency?
Why is it more desirable to have a drug in the body at a lower dose?
Relative potency of two drugs can be compared by :
their ED50 values.
A drug that has comparable effects at lower doses is more potent.
gets into body faster and binds to receptor faster than morphine
opiate- perscribed for cough and wisdom teeth- side effect: constipation
-increases pain tolerance
-Efficacy of asprin is less high
side effects of drugs:
once primary receptors are occupied- search for secondary targets which cause side effects
-secondary effects can be deadly
for drug safety what should you do?
compare ED50 and LD50- where 50% of the people who take the drug are killed- these two areas should not be overlapping (if thereapudic index is small it can kill people!)
TI for alcohol
TI for MDMA
600TI- altered pharmacokinetics by PMMA (it was laced with PMMA which takes longer to get into your system, dont know what you're getting with drugs)
Drug tolerance can develop:
repeated and chronic exposure to drug can result in decreased efficacy/potency.
Increasingly large doses of drug needed to obtain similar magnitude of biological effect that occurred with original dose.
organ systems become more effective at eliminating the drug.
Acetylaldehyde dehydrogenase (ALDH):
metabolizes acetylaldehyde (from ethyl alcohol).
Functional tolerance (a.k.a., pharmacodynamic tolerance)
target tissue may show altered sensitivity to the drug.
Changes in numbers of receptors can alter sensitivity in the direction opposite to the drug's effects:
down regulation or upregulation
continually "bathing" cells in alcohol what will happen?
receptors will be pulled into cell
Agonists ____ receptors:
Antagonists: _____ receptors
is tolerance to a whole class of chemically similar drugs.
E.g., alcohol and barbiturates; act on the same receptor.
occurs when drug effects become stronger with repeated treatment.
E.g., marijuana and cocaine.
refer to factors that affect the movement of a drug through the body.
the amount of drug that is bioavailable (free to act on the target) varies with _____
route of ingestion.
Absorption and distribution
drug must reach target site; may come into contact with cell membranes before entering blood; may need carrier molecule to get to site of action.
route of ingestion: taken by mouth generally has low...
Duration of a drug's effect is determined by how it is _____
Biotransformation: change of the molecule; may result in inactivation and excretion; may increase absorption.
May produce metabolites that are active or could produce side effects.
Drug action is a balance between absorption and excretion.
Absorption may be prevented by selective barriers like:
Lipid soluble drugs pass ____ through cell membranes
Lipid solubility increases absorption of drug- e.g., diacetylmorphine (i.e., heroin) more soluble in lipids than morphine.
More rapid onset and more potent reinforcing properties compared to morphine.
some drugs such as steroids (fat) dont mix well with blood (water based) so what do they need?
what is an example of drug that remains untransformed?
completely same going in and coming out
-used by tribe of barbarians named the bezerkers- their oppononents said they seemed stolid with no emotion
is heroin or morphine more potent?
heroin! slips through membranes
are charged molecules lipid soluble?
Charged molecules (ionized!) are not highly lipid soluble.
Exist as weak acids or bases that become ionized when diluted in water.
Extent of ionization depends upon relative acidity/alkalinity of solution and property of molecule.
Bodily fluid pH- drugs can be dissolved in different compartment of the body depending on pH.
Drugs that are weak acids, ionize readily in _____
alkaline environments and become less ionized in acidic environments.
More ionized = less fat soluble.
Less ionized = more fat soluble.
development of tolderance to hedonic (pleasant) effects of heroin
-BUT other side effects like constipation remain persistent and thinking unclearly
molecule that is ____ can enter almost any site in body
what helps advil get into blood stream?
OJ or grapefruit jucie bc of acidity!
steps of asprin absorbtion
-Non ionized Aspirin passes into basic blood and becomes ionized
-Aspirin is a weak acid
and stays non ionized in
-In more basic intestine,
Aspirin is more ionized.
Decreased passage into
how are leaky capillary's involved in blood brain barrier
blood brain barrier closes them
: absorbtion into GI tract
Highly charged in both acidic and basic environments- poorly absorbed from GI tract.
Curare does not leave digestive tract to enter blood of hunters that eat curare-poisoned game.
The blood-brain barrier
tight junctions within the CNS that prevent the movement of large molecules—can limit drug availability.
-PREVENTS toxic molecules from entering the brain but its also harder to administer the drug
BBB reduces diffusion of :
ionized particles, but cannot impede lipid soluble molecules.
BBB not complete- which areas?
area prostrema (a.k.a., circumventricular region).
"Vomit centre"- senses noxious molecules in blood.
Median eminence- neurohormones released into blood.
form of temporary inactivation.
Drug may be bound by albumin, or bind to muscle or fat...no drug action takes place.
Molecules do not become metabolized or inactivated.
Binding is reversible- drug may re-enter the blood stream.
-no biotransformation, just temproariliy being stored
depot binding results
Reduces drug action at active target...fewer molecules.
Once back in blood stream, concentration is lower and so is the drug effect...fewer molecules.
"Urinary drug testing"- THC can be detected in system for several days/weeks afterwards.
-depots can terminate drug action rapidly- eg thiopental (anathestic drug-- not used for anethesia anymore bc person can wake up during their surgery)
Most drugs affect synaptic transmission: Local anesthetics
block sodium channels and, therefore, block action potentials (and hence pain transmission).
Cocaine first used as an anesthetic: blockade of Na+ channels.
Not Freud's idea to use cocaine as a local anesthetic...Karl Köller (1884).
treats high BP used to be used as antipsychotic-- reserpine in high enough concentrations= parkinsons like symptoms
Presynaptic events are affected by drugs that:
Affect transmitter synthesis enzymes: para chloralphenylalanine inhibits tryptophan hydroxylase (5HT).
Affect transport: colchicine inhibits microtubule maintenance; prevents transport of raw materials to bouton.
Affect storage: Reserpine inhibits catecholamine/serotonin storage in vesicles.
Prevent synaptic transmission: e.g. tetrodotoxin blocks Na+ channels, preventing action potentials.
Alter release of neurotransmitter: e.g. amphetamine stimulates release of catecholamines.
affect either transmitter release or receptor response.
-Caffeine is an exogenous neuromodulator that blocks the effect of adenosine.
-Adenosine: endogenous neuromodulator that normally inhibits catecholamine release...inhibit the inhibitors = stimulation of catecholamines
Caffeine stimulates catecholamine release, causing arousal.
Adenosine is normally released along with the catecholamines and acts on autoreceptors—receptors on the same terminal that released it.
neuromodulators are very
acts as agonist on seratonin receptors and induces hallucinations
chronic alcoholism causes:
receptors to be pulled back into the neuron
-alcohol blocks the ability to fire action potential
-body turns down the amount of GABA that is produced bc alcohol acts like GABA
-why is it a bad idea to go cold turkey? Alcohol is serving as inhibitor and people may suffer siezures from constant firing action potentials if brain is overactive
used to treat bipolar- treats mania aspect. Its a salt, deadly for the liver. It evens you out so you dont have highs
can determine how much to give someone based on height, weight, sex etc.
Par Os (PO)- by mouth
- "by mouth"; most popular--safe, easy, economical.
Drug must dissolve in stomach fluids and pass through stomach walls to reach blood stream.
Must also be resistant to destruction by stomach acids/enzymes.
Absorption: drug must move from stomach to blood stream.
Some not fully absorbed until reach small intestine.
First pass metabolism
drugs taken PO are absorbed into the blood stream and dump into liver (via portal vein).
Potentially harmful drugs are metabolized and inactivated before being sent into general circulation.
May need higher initial doses to achieve therapeutic efficacy- can be dangerous.
if drug is placed lower in rectum, absorbed into hemorrhoidal vein (bypasses liver).
Absorption is irregular--bioavailability hard to predict
liver is involved in:
detox of blood, non specific enzymes for metabolizing- evolutionary for harmful drugs
direct injection of substance into blood circulation; rapid but could be hazardous.
Possibility of overdose or allergic reaction.
IV drug use- increased risk of contracting HIV; safe injection sites.
injection into muscles; slow release- e.g., Depo-Provera (medroxyprogesterone) for contraception.
drug injected through abdominal wall into peritoneal cavity; provides rapid delivery of drug due to increased blood vessels around internal organs.
just under the skin; absorption dependent upon degree of vascularization.
SC implant of hormone pellets.
Inhalation- drug administration
reaches the blood via the lungs; straight to the brain (no "first pass" through the liver); e.g., nicotine and THC.
mucosal membrane of eye, nose, etc; cocaine administered to nasal mucosa produces rapid effects on the brain.
Transdermal- drug administration
drugs that are lipid soluble can pass through the skin; e.g., hormones, nicotine.
injected into the spinal cord; e.g., pain medication.
direct injection into brain; by-pass the blood brain barrier.
can be used to deliver antibiotics at a steady state into brain.
Direct CNS injection of viral vectors for DNA/gene therapy.
absorbtion affected by:
age, sex, body type, time of day
with the use of oil in drugs what effect does this have?
depot binding- stays for longer
Video: drug effects and rat
rat given saline can perform usual task- presses bar every 12sec to get food
-cocaine rat presses it frequently and continuously without respect to time and is crawling all over cage
-marajuana rat is looking into hole waiting for food and pressing bar at random intervals- timing incorrect
STOP STUDYING HERE FOR MIDTERM ONE
Greeks suggested temperament and emotions could be explained by humours— black bile:
Greeks suggested temperament and emotions could be explained by humours—
Greeks suggested temperament and emotions could be explained by humours— yellow bile:
Greeks suggested temperament and emotions could be explained by humours— blood
Hormones (Greek, horman; 'to excite') :
chemicals, secreted by one group of cells, that travel through the bloodstream to act on targets.
release hormones within the body* keep in mind that other tissues like the heart and kidneys secrete hormones too
use ducts to secrete fluids such as tears and sweat outside the body.
or removal of the gonads (usually testes), results in behavioural and physiological changes. First completed by aristotle
Opera singers that were castrated at a young age.- led to their beautiful singing voices but they weren't attracted to females
Father of modern endocrinology:
Berthold: behavioural endocrinology
-Testes release a chemical into the bloodstream that affects male behaviour and body structure.
-Studied rooster's and capons
Berthold rooster examination:
Group 1: left undisturbed, young roosters grow up to have large red wattles and combs, to mount and mate with hens readily, and to fight one another and crow loudly
Group 2: Animals whose testes were removed during development displayed neither the appearance nor the behavior of normal roosters as adults--> small comb and wattles, not mounting hens, not aggressive, crowing weak
Group 3: If one of the testes was reimplanted into the abdominal cavity immdeiately after its removal, the rooster developed normal wattles and comb and normal behaviour-- mounting, agression, crowing
conclusion of Berthold study with roosters
because the reimplantated testes in group 3 was in an abnormal body site, dosconnected from normal innervation, and yet still affected development, Berthold reasoned that the testes release a chemical signal which we would call a hormone, that has widespread effects--> hormone secreted permanently organized external phenotype
*although testosterone must be present early to have such dramatic effects, we would see little change if they were implanted into an adult
Female rodent tests and testosterone
if they injected testosterone after birth, didn't display typical interest in males and there was no regualr release of progesterone and estrogen
-formulated hypothesis: body and brain organize by exposure to hormones in early life and these changes are permanent
-Same hormones "activate" behaviours, but are only short acting.
Forms of chemical communication: Synaptic communication
or neurocrine function—involves chemical release and diffusion across a synapse.
Forms of chemical communication:Endocrine communication
a hormone is released into the bloodstream to act on target tissues.
Forms of chemical communication: Autocrine function
cell produces signal, releases, comes back onto the cell-- short acting hormone communication
Forms of chemical communication: Paracrine function
one cell releases message, affects nearby cells--> no need for transport in blood
Forms of chemical communication: Pheromone function
hormonal excretion to signal other animals of the same species ex) dog and pee
Forms of chemical communication: Allomone function
communication between two different species e.g. flower and bee-- a chemical is released into the environment or skunk and human
Is skunk allomone or pheromone communication?
both! It is released because they feel threatened
General principles of hormone actions:
-Hormones act in a gradual fashion: can last hours or weeks.
-Hormones act by changing the probability or intensity of a behaviour; not an "on-off" switch.
-The relationship between behaviour and hormones is reciprocal- hormones change behaviour and behaviour changes hormones (There is an effect of the environment)
-A hormone may have multiple effects, and one behaviour can be affected by several hormones.
-Hormones often have a pulsatile secretion pattern—in bursts; e.g., cortisol secretion.
Some hormones are controlled by circadian clocks in the brain.
-Hormones can interact with other hormones and change their effects; e.g. estradiol and progesterone in 'estrous'.
-Hormones can only affect cells with a receptor protein for that hormone.
-levels of hormones vary rythmically thoughout the day
Neural and hormonal communications have similarities and differences.
Both neurotransmitters and hormones are stored and secreted by neurons and endocrine glands, respectively.
what hormones does Working memory rely on?
testosterone, progesterone, estradoil
what is cortisol important for?
(peptides used by neurons) can act as neuromodulators--- affecting firing of cell- and alter sensitivity to transmitters
-Found in single celled organisms.
-neuromodulators are a blend of neurotransmitter and (bc they're released into synapses) and hormone (bc they act gradually)
what is ACTH important for ?
flight or fight response
Three types of hormones: Peptide, and Amine hormone:
modified amino acid, smaller and simpler than peptide hormones (modified amino acid)
Peptide: composed of string of amino acids (protein)
Three types of hormones: steroid hormone
4 rings of carbon atoms- derived from cholesterol and enzymes change it into steroid hormone. Highly lipophylic- can travel through membranes- can go anywhere in body it wants to just has to have appropriate receptor in the cell
Hormones exert effects on cells and tissues in the body by:
Promoting proliferation, growth, and differentiation of cells.
"Organizational effects"; thyroid hormones promote cell genesis in the brain and regulate mental development.
Modulating cell activity.
"Activational effects"; e.g., androgens promote survival of new born cells in the adult hippocampus.
Hormones exert influences in two different ways: protein and amine
Protein and amine hormones bind to specific receptors on the surface of a cell and cause release of a second messenger (e.g., cAMP), which bring about changes in cellular function.
Act faster than steroid hormones; action is much briefer.
Hormones exert influences in two different ways: steroid
Steroid hormones pass through the cell membrane and bind to receptors inside the cell.
Steroid hormones act slowly- termed "classical effects".-- can initiate transcription and lead to protein production
Some steroids act on more than one receptor—called receptor isoforms—with functional differences.
E.g., ER alpha and ER beta.
Steroid receptor cofactors
may be necessary for the cell to respond to the steroid-receptor complexes.
Steroids, such as estradiol, can also have a nongenomic effect—a rapid, brief effect involving neuronal membrane receptors.
Difficult to define- steroids are lipophilic.
Testosterone has rapid effects on receptors located in axons and other sites distant from the nucleus.
Contrast with classical, genomic effects.
output feeds back and inhibits further secretion
An autocrine response involves an endocrine gland releasing hormone and feeding back onto itself.
-can have autocrine response (hormone feeds back and inhibits itslef)
-or endocrine cell reacts not to its own hormone but to biological response that the hormone elicits from the target cells
body is a ____ machine
homeostasis, comparable to a thermostat
affects target cell, negative feedback shuts off endocrine cell
Target Cell Feedback
hormone acts directly on its target cells and has a biological effect (e.g., up or down regulate gene transcription).
The biological effect is detected by the endocrine gland, which inhibits further release- 'negative feedback'.
The hypothalamus can direct _____ release
The hypothalamus can direct hormone release—the brain detects the hormone's effects and exerts negative feedback onto the hypothalamus.
The hypothalamus receives a signal from the external environment, which may initiate the cascade.
("directed towards") are pituitary hormones that affect other endocrine glands.
- released by anterioir petuitary
are used by the hypothalamus to control the pituitary release of tropic hormones.
hypothalamus monitors ___ and ___ environment
interior and exterior, stimulates petuitary--> endocrine ---> target---> biological response
multiple points of negative feedback
Specific example of HPT axis
T3 and T4 release by thyroid- important for regulation of growth metabolism
-iodine important for thyroid
-Hypo says to petuitary release thyroid stimulating hormone, release T3/ T4 in presence of iodine
-lack of iodine= goider, T3/ T4 shuts down signal to thyroid
What monitors thirst?
The pituitary gland
(or hypophysis; "outgrowth below the brain") releases important hormones and has two main parts:
Anterior pituitary (adenohypophysis); front of the pituitary; develop from tissue above the mouth (weird, huh?).
Posterior pituitary (neurohypophysis); back of the pituitary; neurons originate in brain.
The two parts of the pituitary gland are separate in function.
The pituitary stalk, or infundibulum, connects the pituitary to the hypothalamus.
Stalk: contains blood vessels and many axons (only extend to the posterior pituitary).
Originate in neurons in the supraoptic nuclei (SON) and the paraventricular nuclei (PVN) of the hypothalamus.
bone around petuitary
what happens if you lost function of petuitary?
fatigue, weight loss, no appetite, loss of sex drive
The posterior pituitary secretes two principal hormones:
Oxytocin is involved in reproductive and parenting behaviour and also in uterine contraction and the milk letdown reflex.
Initiated by suckling—> info from skin receptors sent to hypothalamus—> oxytocin released—>mammary glands release milk.
-Arginine vasopressin (AVP) or vasopressin, or antidiuretic hormone (ADH) increases blood pressure and inhibits urine formation.
Vasopressin and oxytocin can also serve as neurotransmitters in the hypothalamus.
Milk letdown reflex
sucking activates skin receptors connected to hypothalamus
what happens if baby cries around mom?
milk let down reflex
Elevated plus maze
two open and two closed arms, used for test of anxiety in rats
-drop rat into centre and see where they go, takes advantage of 2 behaviours- exploring and anxiety (dont like heights)
-most spend majority of time in closed arms
-DV= % of time in open arms
-spend small amount of time in open arms bc of aniety
-males baseline 30%, vvasopresson injected (causes anxiety) open arm time decreases
no vasopresson in ___ rats
Hypothalamic neurons synthesize releasing hormones.
Axons from these cells converge on the median eminence, above the pituitary stalk.
Releasing hormones are secreted into local blood vessels, called the hypophyseal portal system.
Releasing hormones are carried to the _____
Releasing hormones are carried to the anterior pituitary, which then releases tropic hormones (e.g., ACTH, FSH, LH, etc).
These 'releasing hormones' influence target glands in other parts of the body (e.g., testes, adrenals, etc).
The hypothalamus is influenced by:
1. Circulating messages: other hormones, which may have been secreted in response to release of tropic hormones (may feedback).
2. Synaptic inputs: excitatory or inhibitory input from other brain areas, which can influence the anterior pituitary.
see releasing hormones and theur effects
:) Ch 5 slide 16
Growth hormone (GH):- what substance signals the release of GH?
aka, somatotropin or somatotropic hormone;
Influences growth, mostly during sleep.
The stomach hormone ghrelin ('meal initiator') also evokes GH release.
Ghrelin (acts as a signalling peptide in the CNS) and obesity?
tied to toilet in room during childhood, no one interacted with her, she had stunted growth but began to grow after being relaesed but couldn't talk, cognitive growth= retarded
Stress and Growth
Psychosocial dwarfism is a failure to grow caused by stress early in life.
Somatomedins, hormones that normally aid growth, are released by the liver in response to GH.
Stress (high cortisol levels) and sleep deprivation can interfere with GH release and its normal effects on growth.
Glands stimulated by the anterior pituitary:
1. Adrenal glands,
2. Thyroid gland,
The adrenal glands are located on top of each kidney (renal) and secrete hormones.
In mammals, the outer 80% of the gland is the adrenal cortex, and the core 20% is the adrenal medulla.
hypothalamus detects fear, direct neural connection to adrenal medulla (Dumps Ach onto it) adrenal medulla releases amine hormones- epinephrine and norepinephrine
The adrenal medulla releases amine hormones:
These are controlled by the sympathetic nervous system.
"Fight or flight" response; prepares body for action (e.g., inc. heart rate/respiration).
The adrenal cortex secretes 2 steroid hormones—>adrenocorticoids (adrenal steroids).
1. Glucocorticoids: glucose metabolism; anti-inflammatory.
Cortisol: glucocorticoid stress hormone; high sustained release is harmful (e.g., depression).
anxiety and depresion
Stress/anxiety—> major depression.
Suicide victims and depressed patients: elevated cortisol levels.
Dexamethasone (Another glutocorticoid)
synthetic glucocorticoid; suppresses cortisol release in normal people but not in depressed patients.
Dexamethasone suppression test
depression men vs women
More women than men suffer from depression.
May reflect patterns of help-seeking; women go to doctors more than men; not entire story.
Gender differences in endocrine physiology, related to the menstrual cycle.
Postpartum depression immediately precedes or follows childbirth.
The adrenal cortex secretes 2 steroid hormones: Mineralocorticoids
are adrenal steroids that affect ion concentrations in tissues.
Example: Aldosterone acts on the kidneys to retain sodium to reduce amount of urine produced
Adrenal cortex also produces Sex steroids
such as androstenedione, are steroid hormones produced in the adrenal cortex.
Androstenedione contributes to the adult pattern of body hair in men and women.
what happens with sustained cortisol?
immue system falters, leads to depression
Baboons and stress
-live in stressful heirarchy
-survive through aggressiveness
-measured stress hormones in baboons
-submissive: high stress hormones inc heart rate, boold pressure, poor immune/ reproductive system, brain chem off
-nearly half males in troop died when they were exposed to contaminated meat
-aplha male died, "nice guys" were left and lead to peaceful society thereafter
--unless you're alpha male, constantly stressed out
-new baboons joining the group reaklized they had to adjust their behaviour
what is happening with the HPA axis in depressed people?
it doesn't work, out of control
sex difference in depression
fairly stable until woman past reproductive years, think that antidepressant medication will return HPA to normal functioning
Thyroid-stimulating hormone (TSH) is secreted by the pituitary.
Its release is controlled by negative feedback from blood levels and by thyrotropin-releasing hormone (TRH) from the hypothalamus.
Recall: TRH causes the thyroid gland to produce thyroid hormones (T3 and T4). What else does the thyroid produce?
The thyroid gland also produces calcitonin which promotes calcium deposition in bones.
Discovered at UBC!
cretinism and hypothyrodism
lack of foods rich in iodine- cause thyroid to work over time swelling into a goiter!
Early thyroid deficiency can result in cretinism, or congenital hypothyroidism, accompanied by mental retardation.
-treated with iodine
Why is calcitonin important?
what do you need for kisspeptin to be released?
Steroid Production and Release: Gonads—ovaries and testes
produce sex steroids.
the _____ controls gonadal hormone production by releasing gonadotropin releasing-hormone (GnRH)
-GnRH stimulates the anterior pituitary to release FSH or LH.
GnRH neurons are stimulated by a hypothalamic peptide, kisspeptin, which is involved in?
the onset of puberty.
The hypothalamus also uses gonadotropin-inhibiting hormone (GnIH) to inhibit:
gonadotropic secretion; anti-GnRH.
testosterone important for memory formation (STM) in the ___
what sex charateristics is testosterone important for?
secondary sex characteristics (body hair, breast size)
testosterone and mental disorder
sex differences in incidence suggest role
Androgen production decreases as men age; increased risk for
Androgen replacement is
risky can lead to prostate cancer; best to use SARMs- relatively new
Ovaries produce hormones in cycles—
progestins, such as progesterone, and estrogens such as 17β-estradiol (estradiol).
1. Reproductive related behaviours
HPG Axis in females (see pg 147 for male and female version)
-Note: ovary produces
T; 85% converted to
-Role of T in females? Similar to men- facial hair, lower voice
-Loss of LH/FSH signalling?
-it is detected in pregnancy tests, this is HCG
"possessed by the gadfly"; ovarian hormones regulate reproductive cycle.
Humans: ~4 weeks; follicular and luteal phases; E2 and P peak during release of egg.
Rats:4-5 days of estrous; same peak in E2 and P; no pseudopregnancy phase.
Estrogen replacement therapy (ERT): post menopausal hormone therapy.
Cognitive improvement after taking the hormones evident.
-depends on several factors, one of which is timing of HRT following menopause.
Most popular? Premarin (actually makes cognition worse but it is unknown by general public)
No steroid is found exclusively in either males or females;
rather, the two sexes differ in the proportion of these steroids.
Receptor distribution/regulation is important- differs between the sexes.
Exposure during development to hormone also has imp. organizing effects.
Testosterone is an important precursor for making estradiol.
An enzyme, called aromatase, converts testosterone to estradiol in a single chemical reaction.
Testosterone is also converted into a more potent androgen, dihydrotestosterone, via 5-alpha-reductase.
be converted to
or DHT; DHT cannot be
converted to E2 and vice
act via the androgen
single gland on top of the brainstem.
It secretes an amine hormone, melatonin, almost exclusively at night.
Binds to a GPCR in the cell membrane.
Melatonin provides a signal that tracks day length and the seasons.
peaks of melatonin
mostly at nighttime, used for jetlag but it has been shown ineffective
Melatonin controls mating
in hamsters (seasonal
Short days (winter): increased melatonin secretion results in shut down of GnRH.
Gonads atrophy (crudessence)
Long days (summer): less melatonin; testicular re-crudessence.
Pineal gland sits atop bird brain, underneath thin skull.
Contains photosensitive cells to monitor day/night cycles
- Similar situation in lizards (not surprising given evolutionary lineage).
Hormones play a role in social behaviour:
Oxytocin and Vasopressin: peptides differ by only 2 amino acids.
Oxytocin is released during nursing interaction and during orgasm.
Both involved in social behaviour.
Highly conserved evolutionarily.
Vasopressin and voles
Important for affiliative behaviours in rodents—> in particular voles
monogamous; form pair bonds. oxytocin infusionsin females! vassopressin in males!
dont form pair bonds, polygamous, large hippocampus, far fewer vasopression receptors
PV's form bonds; MV's do not...unless induced to
subtle difference in sequence encoding the gene.
results in increased expression in hippocampus and more activation of amygdala in a face recognition task.
VI receptors in meadows voles
expressing a VI receptor in meadow causes formation of pair bonds
-if you inherit both long forms from parents activity in amygdala is high -- for face reception
Techniques in behavioural endocrinology:
compare which behaviours are different in animals lacking specific genes versus normal animals.-- can have social amnesia
Techniques in behavioural endocrinology: Knock in ("transgenic") organisms
can look at behaviours in animals expressing genes from other organisms.
Oxytocin and Social Recognition
Social recognition: scent based—> novel versus familiar.
No social recognition = long time smelling familiar conspecific.
KO of oxytocin gene = male mice with social amnesia; spent equal time with familiar and novel female.
Oxytocin treatment of OTKO mice = more physical contact with novel female.
Hormonal and Neural Systems Interact to Produce Integrated Responses
Integration is the key.
Hormonal and neural systems work together to regulate behaviour.
E.g., mating in male ringdoves.
The hormonal and neural systems exert reciprocal influences on each other.
Experience affects hormone secretion, hormones affect behaviour, and behaviour affects future experiences.
Hormone release affects physiology; change in physiology affects hormone release.
Mating in ring doves- interactive signals between the nervous sytem and the enodcrine system
female behind glass, male placed infront of her- activates retina which activates hypothalamus, releases GnRH, activates petuitary, releases FSH and LH, testes release testosterone and ring dove does a dance. His behaviour changes hers- stimulates her hypothalamus and causes release of hormones like estradoil
what common quality is seen across all different species in regard to sex?
phenotypic sex differences- males are always larger
examples of men and women's different behaviour
packing (women take longer, men right before trip), women think they look fatter in the mirror etc
sex difference in disease: depression
women have higher rates of depression but this effect goes away after gonads seize releasing hormones
sex difference in disease: alzheimers
women have higher rates
how are vertebrates linked evolutionarily?
brains share the same basic shape
sex difference in disease: parkinsons
more common in men
does evolution continue today?
old idea about species and evolution- what was this concept called
Until about 200 years ago, it was believed that species were created separately; i.e., not connected to a previous form or "common ancestor"; concept of stasis-staying the same. This was corrected by the naturalists who study forms and classification
students of animal life and structure, began to doubt this concept of stasis and that all species were created seperately. They noticed that limb bones of all mammals are markedly similar-- just modifications of a single plan to adapt to different environments
Linnaeus and levels of classification
developed classification system to catalogue species diversity. 1st name is genus and second name is species. Order of classificiation: Kingdom, phylum, class, order, family, genus species
suggested animals adapted to environment.
explained how this adaptation could've occurred.
Lamarck and giraffe theory
thought that giraffes started with short neck but then had to adapt to environment and reach high tree branches, eventually had a long neck after alot of stretching
what did new formations in the brain over evolution result in?
homology of forelimb structures
human arm, dog forelimb, seal flipper, bat wing (Showing a degree of similarity (e.g. in position, structure, function or characteristics) that may indicate a common origin)
Lamarckian evoltuion 4 ideas
-said evotuion started simple then moved to complex organisms (correct)
-Animals do not become extinct (incorrect)
-Change in environment brings about changes in
-Acquired characteristics are passed on to the next
generation. (not correct)
Darwin and Wallace proposed evolution by natural selection—a theory that says evolution proceeds by differential success in reproduction. (idea came to wallace when he had a fever, Darwin had been gathering research for the idea for years)
"decent with modification" - birds evolved from dinosaurs-- archaeopteryx found to have feathers and evolved into birds
Reproduction will increase a population rapidly unless factors limit it.
Individuals of a species are not identical.
Some variation is inherited.
Not all offspring survive to reproduce.
increase the likelihood of having offspring.
Resources are scarce—> those better adapted, survive and reproduce.
"Survival of the fittest".
-Darwin also inferred that variations affect the probability that they will survive and reproduce.
Theory of Evolution is fact
just like gravity!
anatomical and behavioural features are selected for by opposite sex.
Exerts a "selective pressure" to be sexy. e.g. ornamental tails of peacocks
red deer and sexual selection
antlers used during mating season to fend off other males and gain more access to females
male peacock and sexual selection
impressive feathers with long tails- higher mating chance
sexual selection and hair
men selected for less hairy women-- evolved this way and women selected for more hairy men
what likely drove evolution for brain size?
Competition between males likely drove the evolution of brain size
--In monogamous species (Homo sapiens), larger brains were selected for, and not testis size; may needed larger brains for "greater social acuity" (i.e., deception)
evolution and brain size in bats
-In polygamous species, such as bats, larger testis size was selected for whereas brain size was not; more sperm.
bigger brains are better but...
only to a certain point (have to account for body size)
-smaller brain in polygamous mating system
-larger brain in monogamous mating system
studying other species and comparing them to humans.
offers a "natural experiment"; how did animals adapt to their different niches?
-Successful homo sapiens with big brains outcompeted males with smaller brains—> passed "braininess" on to offspring.
what part of the brain is compartively larger in humans than other animals?
what part of the brain is compartively larger in sharks than other animals?
brain regions for olfaction
sexy clothes study
-looked at choice of clothes in university females during ovulation--> wore more revealing clothes during ovulation, when not ovulating choose less sexy clothes 13% effect size- 13% of the variability in sexy clothes choice is accounted for by ovulation time
shows similarities in behaviour or structure among unrelated animals due to adaptations to similar environments.
resemblance between features (body shape), due to convergent evolution.
-e.g. dolphins and cows very close relatives, shows divergence- some migrated out of the water (divergent evolution)
is a similarity based on common ancestry (e.g., forelimbs).
refers to similar function even though a different ancestry—a human hand and an elephant's trunk/octopus arms are analogous even though they look different.
eyes have evolved at least..
Evolution considers genes/genetics. ____ is building block of evolution.
-Background radiation and "copy errors/expansions" are ubiquitous.
-Two main players: Mendel and DeVries in genes
Mendel provided this break through by studying genetic transmission in peas- crossed different types of peas to see offspring outcome- formulated the laws of biological inheritance. His work largely ignored until DrFries-- he noted occasionally a new feature arose spontaneously, a mutation, and is passed onto successive generations by studying primroses.
studied prim rose- put two prim roses together- unlikely to seed different sturcture but every now and then mutation arose- he observed this and introduced idea of mutation and that it drove evoltuions- can happen in relatively short time from one generation to the next
are spontaneous changes in genes; can be passed on to the next generation; adaptations!
May be harmful, neutral, or beneficial (called conspecifics) when beneficial.
What about behaviour? How is it contributed to by genetics?
Genes control behaviour—> monogenic inheritance affects mating in flies (if dance is good enough then they can mate with females, "fruitless gene" controls this dancing behaviour),
-Mutation of the gene changes mating dance and results in poor copulatory behaviour; males with fru mutations do not mate.
-monogenic inheritence not often seen in humans
sex determining region of y
how does sry gene work
in a male, there is and X and Y chromosome, which contributes to production of testosterone, Binds to AR; masculinization of external phenotype and brain.
androgen receptor mutation (androgen insensitivity)
- Androgen receptor mutation
(non functional protein- can't
of external phenotype and
in the female phenotype this means they will be attracted to males, cant reproduce, have testes in stomach, no menstruation
what happens is there is no sry gene?
default female phenotype
Simple Mendelian inheritance: androgen receptor
XAR (from mom) and XAR (from dad) produces a female who is attracted to males
XAR (From mom) and Y from dad produces male attracted to females
Xtfm from mom and XAR from dad = female, attracted to males
Xtfm from mom and Y from dad= female, attracted to males but no reproductive capacity
-tfm: testicular feminization
how many chromosomes do we have?
what are hemoglobin genes?
carry oxygen= essential genes, shouldnt be too much selective pressure on them
Initial mutation creates 2 new phenotypes.
-One phenotypes is
unsuccessful-- dies off
-Adaptive mutations are favoured and spread, genes are unstable
-Mutation in Genes associated with intellectual disability
constantly bathed in cosmic radiation from the stars and universe- can effect our DNA and sometimes leads to genes being edited. Deleted base= frameshift!
Nucleotide excision repair
Sometimes errors are produced...changing the DNA sequence.
-problems with the repair mechanism-- spontaneous mustations
Trisomy 21 (down syndrome)
extra chromosome on 21
Modern Evolutionary Theory
Combine Darwin's principles for natural selection and modern genetics to understand how species can change and adapt.
-If mutation results in better adaptation = increased fitness.
-Natural selection acts on these mutations = evolution.
Taxonomic classification: science of classifying species.
Classification rests on defining groups by shared characteristics.
pulling apart of chromosome that usually occurs doesnt happen, both chromosomes go into one cell
In Linnaeus's system of classification, each species has two names:
Genus—a group of species that resemble each other.
Species—a group of individuals that can interbreed and produce fertile offspring.
We are Homo sapiens; contrast with Homo neanderthalensis or Homo habilis.
He was a christian who thought that he was uncovering the hand of god
Why Classify species?
Different species show different solutions to environmental changes.
Living animals, along with fossils, allow study of the body and brain.
Can make inferences about origin of behaviours.
-understand relationship between organisms
Linnaean Classification of the Domestic Dog
Kingdom: animals--> Phylum: vertebrates --> Class:mammals--> order:carnivore--> family: canine--> genus: canis--> species: canis familiaris
___________uses genetics to determine phylogeny.
Taxonomy uses genetics to determine phylogeny (evolutionary history of a particular group of organisms).
A ___ can help date an organism.
___ can quantify the differences between species and also estimate their divergence from a common ancestor.
rate of DNA change; mutations occur at a relatively steady rate.
Gives an estimate of how long ago species diverged from a common ancestor.
we share 99% of DNA with chimps and bonobos how are we so different?
different genes get expressed, expression at different times, amount of protein produced is different
what do bats use to hunt?
ecolocation, humans cant hear it
Why Should We Study Particular Species?
Can study different species from an evolutionary perspective to understand how they adapt to a particular environment (niche).
Each adapted species will have developed behaviours and neural mechanisms that allowed them to exploit certain niches.
Conservation of mechanism across phylogeny".
studying dopamine receptors in rats that can be used to related to humans
Evolution and the brain
Adaptive pressures select for certain brain structures that give a species a selective advantage.
Successful species reproduce and pass along the brain structures to successive generations.
Reasons to study certain species:
Outstanding features, like sensory skill: e.g., hearing in owls.
Convenience: laboratory rodents (rats and mice).
Comparison: differences in seeing in new world monkeys. "Sex differences" in humans.
Preservation: help conservation efforts.
Economic importance: BC salmon.
Treatment of disease: Ebola; SIV (monkey equivalent of HIV, studying it can lead to treatment in humans)
Evolution of Learning and Memory
An important behaviour that arose was the ability to learn.
Allowed the ability to predict how to find food and avoid predators.
the capability to change behaviour following important experiences.
evolutionary to learn because...
learn about safe and dangerous food sources
Can study how memory works in simple invertebrates; who has been a main prototype?
Aplysia californica.-- sea slug
Invertebrate nervous systems:
Fewer, larger, and more complicated neurons for information processing,
Ganglia: located at midline.
Giant axons (myelination in vertebrates).
Specialized sensory systems for escape behaviour.
Tend to be built around the gut.
Brain differences often related to:
behavioural complexity/social structure. (e.g. rats and mice live in demes)
Anatomical differences tend to be quantitative in nature—> larger brain region, bigger neurons, etc.
Can study memory in animals that are exceptional at remembering; e.g., nut caching squirrels and birds. why do these animals cache?
cache in fall for scarce winter months
hippocampi are large- used for spacial navigation and memory-- thought that they have large hippocampi to allow these behaviours and also their hippocampi grows as a result
Can study how memory works in simple invertebrates; who has been a main prototype?
Aplysia californica.-- sea slug
Brain Adaptations in Birds: Behavioural Specialists
In some species of songbirds, song repertoires are adaptive behaviours.
There is a strong correlation between repertoire size and HVC size (brain region important for songs production in birds)
Selective pressure on songbirds
females choose males with complex songs
What does HVC do in young songbirds?
cortical structure, youner birds store older birds songs
HVC is much larger in birds that have ___
complex bird songs
Selective pressures shape a species: sumurai crab
looks like samurai mask so fishers didn't want to eat it- they always wanted to throw it back
-this was a selective pressure
Mammals' lifestyles are related to cortical organization- comparisson of rodents like rats and squirrels and platypus
Nocturnal rodents (like rats) that use whiskers have a large part of their cortex devoted to their whiskers but much less to vision compared to diurnal rodents (like squirrels).
-rats- each whisker has barrels that correspond in brain-if you clip individual whiskers- surrounding barrels take over this area
-The platypus uses its bill to detect mechanical and electrical stimuli; most of its somatosensory cortex is devoted to the bill.
All Vertebrate Brains Share the Same Basic Structures
The main brain structures are the same in all mammals (and other vertebrates).
The relative sizes, proportions, and anatomical locations of structures have been subject to evolutionary modification to allow adaptation to niches. All include visual cortex, auditory cortex, somatosenesory cortex
Each of the main structures in the human brain has a counterpart in the rat brain. What is the difference?
Differences between human and rat brains are in actual and relative size of regions, such as cerebral cortex and olfactory bulbs.
-difference in size!
Vertebrate nervous systems share certain main features:
Develop from a hollow dorsal neural tube
Segmentation: spinal nerves extend from each level of the spinal cord.
Hierarchical control (brain controls body)
Separate peripheral and central nervous systems
Localization of function- certain functions are controlled by certain locations in the central nervous system
What brain regions do all vertebrates have?
visual, auditory, somatosensory cortex
veretbrates and relation of body size, brain, and neurons
In general, vertebrate species with larger bodies tend to possess larger brains, with larger neurons, and larger dendritic trees.
brains and evolution. Where do the differences among vertebrate species brains lie?
The brains of our ancestors increased rapidly in size. The difference of different vertebrates brains lies not in the subdivisions but in the relative size.
Two methods are used to study evolution of the brain:
1. Endocast—uses fossil skulls to make a cast of the brain to give a reasonable indication of the size and shape of the brain, but no fine detail.
2. Living animals: choose living animals with similarities or differences from ancestral forms
-allows for the study of the internal structure of the brain: the nuclei, fibre tracts, and circuitry.
E.g., opossums resemble fossil mammals from 50 mya more closely than present day mammals.
Through evolution, vertebrate brains have changed in both size and organization- what about the cerebellum?
Cerebellum is larger in mammals and birds but tiny in lampreys (a very basic organism).
Important for enhanced sensory processing and increased motor agility.
Lampreys do not need to be acrobatic, throw a spear, navigate terrain from above.
study of Einsteins brain
found in jar, corpus callosum was larger in Einstein- is this causal? no correlational
--he sat in an armchair and theorized, maybe this inc the size or maybe he was born with it which made him smart
The differences are not in the basic subdivisions but in their relative size, and _______
All mammals have a six-layered cortex, also called
who had the first cerebral cortex?
Reptiles were the first vertebrates to have a cerebral cortex; only 3 layers.
Analogous to the three-layered hippocampus in mammals.
The encephalization factor (K):
measure of the deviation from best fit line of brain size relative to body size.
Brain weight to body weight: "line of best fit" = 0.7; relationship common amongst vertebrates.
K is a measure of how close (far) are each species is to this regression line?
-error variance demonstrated by humans on best fit line graph
constraints on brain size?
birth canal, energy consumption
Brain evolution shows size changes both in specific regions and overall.
The size of each brain structure is highly correlated with the total brain size.
However, the rate of increase in some brain areas can differ between small and large brains.
-cortex far suprsaed all other brain regions in size- grew extentially past other structures such as the medulla
In primates, brain regions that develop later have enlarged more than earlier regions.
Larger brains have evolved by prolonging the later stages of development.
In humans, this may explain changes in the cortex, where new neurons form the outermost layers.
Cortex is important for planning and regulating complex behaviours.
gene is important for migration of neurons
-they grow up the cortex
less complex, less gyri, simplistic behaviour due to mutation of RELN gene, its recessive
Hominid brains enlarged rapidly in our recent evolution: Australopithecines
were hominids that made and used tools; tool use arose about 2.5mya.
Tool use- reduced the necessity for large jaws and teeth, and those became steadily smaller.
-Chimps use tools (rocks) to crack nuts.
which happened first- brain size or complex behaviour?
-Homo sapiens brains tripled in volume!
-Brain size increased first- modern culture second.
A large brain has costs and benefits:
A long gestation period- difficult birth.
Prolonged dependence on parents- altricial.
High metabolic cost- 2% of our weight, but 30% of our metabolism goes to maintaining brain.
Complex genes vulnerable to mutation- a lot can go wrong.
Social brain hypothesis:
larger brain needed to maintain social relationships between similar individuals.
Primates show a correlation between clique size (a group of individuals that regularly socialize with one another) and size of the cortex relative to overall brain size.
Mean clique size increased to ___ in humans
150, perhaps our brains are too small to keep tabs on more than 150 people
Larger Brains are More Social
Adaptive advantages of a large brain include increased survival and ability for group interaction in humans.
Innovative behaviour, use of tools, and social learning (learning by watching) in 116 primate species.
Positive relationship between forebrain size and these behavioural indices.
Jap Macakcs (monkeys)
wash their fruit, improvement in overall health
Very similar genomes can produce different brains.
-abnormal spindle-like microcephaly-associated protein
Influences the size of the cerebral cortex. Humans who inherit the one bad version are devlopmentally disabled.
Gene differs considerably in humans compared to chimps—different form of same gene= big changes in behaviour.
Expression of genes also different in humans: similar in the blood; big difference in the brain.
Comparison of Gene Expression
-Differences in gene expression reveal the extent of similarity between species.
-For example, comparisson of human and chimp brain: the DNA sequences of specific genes may vary in important ways between the species, and humans and their non human relatives may also differ in how are genes are expressed
differences in the amount of beta catenin
-more beta catenin- larger brain in mice
Some evolution can be rapid:
Overuse of antibiotics speeds evolution of resistant bacteria.
-big horn rams - hunters prefer rams with big horns and overtime this have evolved into rams with smaller horns
Radiocarbon dating- colonization of europe
shows the colonization of Europe and Asia by Homo sapiens 50,000 years ago.
-Differences in skin colour, facial features, and stature of inhabitants of those regions have occurred since then, in response to climate conditions.
Colonization of Europe and Asia
50k years of evolution!
Prion disease in cows; bovine spongiform encephalopathy (BSE or 'mad cow' disease).
Prions (bits of RNA) responsible for the outbreak of vCJD in humans.
Fore ("for-ay") people in Eastern Highlands of Papua New Guinea- Kuru ("to shake").
Ritualistic eating of brain of dead- typically wife.
-Variation in the prion protein gene (PRNP) called G127V in surviving tribe members- confers resistance.
Not all changes in recent humans are evolutionary, or even genetic.
Modern medicine has prolonged life expectancy and can also reverse infertility (sometimes).
May artificially change genetic make up of population.
-As long as we all don't make equal contributions to next generations, evolution is still occurring in humans.
The mature human brain has ______ neurons (plus glia!).
The developing nervous system relies on ____ and its _____.
The developing nervous system relies on genetic information and its environment.
massive proliferation of cells- ---> gastrulations and ectoderm, endoderm and mesoderm
primitive streak becomes?
CNS, cells around neural plate divide- leads to development of CNS
what does NOTOCHORD do
rodlike sturcture that forms on the midline
neural groove forms the _____
neural groove forms the neural tube
The anterior part of the neural tube has three subdivisions:
forebrain, the midbrain, and the hindbrain.
6 steps in CNS development
1) neuronogenesis- cell division, proliferation) 2) migration 3) differentiation- when arrive at particular location they become a particular type of neuron 4) synpatogenesis- form connections 5) apoptosis- cell death bc more cells are made than are needed 6) refinement- ones that get proper nourishment last, those that dont die
marginal zone is the ___ of the brain
ventricular zone is the ___ of the brain
The Proliferation of Cellular Precursors of Neurons
neural precursor cell divides into two daughter cells, one cell eventually becomes a neuron and the other goes back to the inner surface in the ventriuclar zone
cells move away from the ventricular layer, where they were originally formed
Cell adhesion molecules (CAMs) :
A protein found on the surface of a cell that guides cell migration and or axonal pathfinding - genetic abnormalities in CAMs can disrupt cell migration, which can result in a vastly reduced population of neurons, disorderly arrangement and behaviour disorders
once cells reach destination what happens?
Once cells reach destination, differentiate into cellular phenotype; terminal or differentiated cell fate.
Invertebrates and vertebrates handle this differently
C. elegans (nematode): and neuronal development
researchers can follow the development of every neuron (only 302); the cell fate is highly determined.
Each cell expresses a certain set of genes, which specified what the cell is to become, also depends largely on what cells it is next to
Differentiation shaped by ______ in vertebrates
cell-cell interactions; less predetermined, it is not a hard wired process.
Gene transcription is involved.
Two types of influences on differentiation:
Cell-autonomous—independent of other cells and driven by genes, intrinsic organization as seen in vitro (in cell culture).
Non cell-autonomous—neural environment; cells are affected by the influence of other cells.
What a cell becomes is affected by it's position in the developing CNS and what cells are around them.
how do precursor cells migrate?
across radial glial cells out of the ventricular zone
Production of motoneurons:
differentiation based on the neural environment (i.e., cell non autonomous).
Cells in the notochord release a protein (Sonic hedgehog; Shh) that directs some cells in the spinal cord to become motoneurons.
is the influence of one set of cells on the fate of nearby cells.
Slit prevents axon from __
coming back to original side once it crosses the midline, its a chemorepellent
Cells differentiate into the appropriate cell type for their _____
is the response to cell injury in development; other cells will develop and take its place. e.g. if cells from a chicks limb are removed before hatching, other cells will pitch in to replace these cells and the chick will be hatched normally with no impairment
are undifferentiated cells that can divide, and their daughter cells can assume a new cell fate.
Brain cells change early in life through:
Process outgrowth—the growth of axons and dendrites.
Synaptogenesis—formation of synapses.
Extensions emerge from growth cones at the tips of axons and dendrites.
Filopodia- what do they adhere to?
are the fine outgrowths of growth cones (kinda like fingers on your hand).
Filopodia adhere to CAMs in the environment and pull the growth cone in a particular direction.
Axons are guided by chemicals released by the target cells: Chemoattractants
1. Chemoattractants are chemical signals that attract certain growth cones.
Axons are guided by chemicals released by the target cells: Chemorepellents
Chemorepellents repel growth cones.
chemoattractant; directs axons to cross the midline
(a-cell grows in presence of NGF; b-asymmetric growth in presence of NGF; axons repulsed by semaphorins).
what is NGF?
nourishment factor for cell growth
Synapses form rapidly on dendrites and dendritic spines.
Spines proliferate after birth, and connections are affected by experience (e.g., vision).
The nerve cell body increases in volume to support the dendritic tree
Ontogenic Cell death (apoptosis):
a normal part of development.
Cells have "suicide genes" and "programs" that are expressed only during apoptosis.
Apoptosis is highly regulated and well orchestrated; prevents cell contents from spilling into extracellular space.
Caspases (cysteine requiring aspartate proteases):
family of enzymes that "cut up" proteins and DNA; "initiator" and "executioner" proteins.
What do bcl2 do?
Bcl-2 proteins block apoptosis by preventing the release of Diablo.
Bcl-2 belongs to a family of pro-survival proteins; prevents cell death...promotes survival ("oncogenic").
slide 39 of lecture 1 chapter 7
a type of death gene, caspases are a family of proteases (protein dissolving enzymes) tgat cut up proteins and nuclear DNA. everything is encapsulated in membranes while degredation occurs
why is light required for development of visual system?
w/o light, dendritic spines wont form other cells from other eye will liekly take over
Several factors influence cell death in the nervous system like?
If the size of the synaptic target is reduced, fewer neurons survive.
released from target cells. Neurotrophic factors "feed certain neurons" to help them survive.
E.g.'s- Nerve Growth Factor, Brain Derived Nerve growth Factor, Ciliary Neurotrophic factor.
Nerve growth factor (NGF)
-nourishment for cell growth; it is produced by targets and taken up by the axons of innervating neurons, keeping them alive. Produced in the spinal ganglia and ganglia of the sympthetic nervous system
The Effects of Nerve Growth Factor
-activation of neutrophin (prevents neurons from dying) receptor increases chance of
survival, no neutrophin = apop.
A Model for the Action of Neurotrophic Factors
-target cells make different neutrophic factors
-neutrophic factors are taken up and transported to soma; this affects growth of neuron.
-cells that are outcompeted for neutrophic factors die via apoptosis.
-synapses also compete for neutrophic factors; active ones stick around; outcompeted ones are 'pruned'.
or synaptic remodelling, refines synaptic connections.
One influence on synaptic survival is neural activity.
A neurotrophic factor may contribute as well
rats visual cortex and postnatal development of synapses
synaptogenesis peaks around 16 days- largely bc theyre born with their eyes shut and neural connections form quickly once their eyes are open
when do a large number of disoders arise in humans?
when synaptic pruning ends around late puberty to early adulthood- last to develop is the prefrontal cortex- late maturation may explain teenagers impulsivity
Synaptic Remodelling in Humans
In humans, synaptic remodelling is evident in thinning of the gray matter in the cortex as pruning of dendrites and axon terminals progresses.
The thinning process continues in a caudal—rostral (i.e., back to front) direction during maturation.
Suggests prefrontal cortex matures last.
Intrinsic and extrinsic factors important for connectivity; studied frog eye sight.
-three eyed frog has two eyes innervating the left tectum
-innervation pattern shaped by experience: silence one of the eyes and no alternating pattern would exist
-TL/DR: chemical cues attract axons, synapses
established and maintained by activity.
-Similar process takes place in young mammalian
cells during development.
Supports the chemoaffinity hypothesis
The chemoaffinity hypothesis says each cell has a chemical identity to guide development at a synapse.
when can amphibians recover from brain injury?
two possible mechanisms of chemoaffinity
1) find cell with "chemical
address"—innervate, After re-innervation, connections (synapses) are fine tuned by
2) follow a gradient of chemical cues —innervate.
impairment of vision in one eye with inability to see clear forms.
-People see a double image due to one eye being misaligned.
Can be corrected if eye is realigned- this must take place in childhood; ineffective if done in adulthood
no light to both eyes-produces changes in neurons in the visual cortex (loss of spines and a decrease in synapses). Will result in blindness, if deprivation lasts long enough they will never regain sight
The sensitive period of development :
The sensitive period of development is when experience or treatment can make permanent alterations.
during the sensitive period of development causes the deprived eye to not respond in adulthood.
Experience and Brain Development and cortical neurons responding to light in the eye
Normally, most cortical neurons respond equally to light presented to either eye.
In development of the visual cortex, axons from each eye compete for synaptic targets.
ones in which neurons are talking to each other, predominate. Inactive ones are pruned.
Occluding an eye inactivates the synapses and they retracted (i.e., pruned).
grow stronger or weaker depending on their ability to affect a postsynaptic cell.
added throughout life; provide myelination; speed APs up allowing large ensembles of neurons to communicate with each other.
Biphasic: in humans around 24 weeks post conception; most intense phase just after birth.
First region to display myelination- spinal cord.
Sensory zones myelinated before motor zones in cortex; sensory function matures before motor function.
-Not just myelination; integral to normal development of nervous system.
is a rare disorder caused by a mutation that disables a gene called MeCP2 and its protein. May lead to autism or never developing speech, males almost always die before birth and girls have these drastic outcomes.
Absence of the protein disrupts development in many parts of the body, including the brain.
Thought primarily due to loss of MeCP2 in neurons (incorrect assumption). ** actually due to lack of MeCP2 in glial cells!
Rett syndrome and KO mice
Global MeCP2 gene KO mice- decreased brain growth; may be caused by the absence of MeCP2 protein in microglia (recall: clean up debris in the CNS).
Global MeCP2 KO mice normally die at 11 weeks.
Irradiation + injection of normal microglia (with expression of MeCP2) in global KO mice = normal brain development and behaviour.
Irradiation + injection of KO microglia (no MeCP2) = death at 11 weeks of age.
how does gamma radiation effect glia cells?
wipes them out, can inject healthy bone maroow to get healthy microglia after
"Resuce of function experiment" in KO mice
open feild test: behavioural assay- put mouse in box and camera tracks thier activity. Results: tons of exploration in normal control (no area unexplored), KO mice with KO microglia- dont explore their environment, they are anxious and nervous so they stay at the edge, also seen with KO mice with no microglia, KO mice with normal microglia that have been rescued - restores environment exploration and their typical behaviour
Fetal alcohol sydrome impaired structures in brain
corpus callosum underdeveloped
Astrocytes important constituent of blood brain barrier.
Tight junctions and many of the transport mechanisms (both inward and outward) are already present in early in development.
Vascular Endothelial Growth Factor (VEGF): important for BBB formation; KO and no BBB
Intellectual disability and envionmental factors that can limit brain devlopment
refers to a variety of conditions that impede mental growth.
Environmental factors can limit brain development:
1. A transient lack of oxygen at birth—hypoxia—can affect the brain; induces apoptosis.
2. Undernourished mothers may have underweight children who may also suffer from other brain abnormalities.
3. Viral infection and drug exposure can produce developmental disorders.
studies pathological effects of early exposure to toxic substances.
Fetal alcohol syndrome (FAS):
a developmental disorder caused by maternal ingestion of alcohol.
is characterized by impaired social interactions and language and a narrow range of interests and activities.
Children may perseverate, showing a behaviour repeatedly.
There are structural differences in the brain (e.g., reduced corpus callosum and cerebellar regions)
Amygdala contains fewer cells; associated with fear and suggests autistic children find eye contact aversive.
People with autism may be unable to empathize with others.
They have difficulty trying to mimic movements or facial expressions.
There is low activation of a frontal cortex area containing "mirror neurons".
what brain pattern is characteristic of people with autism?
underactivation of mirror neurons
Autism: shown pictures of family and brain response
brain activation abnormal
what are mirror neurons important for?
mimicking actions and empathy- social cohesion
is sometimes called high-functioning autism.
Children with Asperger's do not lose their language capabilities.
They have difficulty interpreting emotional facial expressions in others.
Men are...Good systematizers, poor empathizers (Baron-Cohen...yes, "Borat's" cousin).
is a disorder of protein metabolism; "inborn error of metabolism".
The defect is the absence of an enzyme that metabolizes phenylalanine.
If not corrected by diet, high levels of phenylalanine will cause intellectual disability; build up is toxic to brain.
Foods high in phenylalanine? Only the tasty ones...salted/cured meats, BBQ.
are genetically identical animals, yet neurons in clones can show differences in neural connections.
Genetically identical individuals can show differences in behaviour; concordance rates and homosexuality—not 100%.
the study of factors that affect gene expression, without changing the nucleotide sequence of the genes.
An important epigenetic factor that affects brain development is ______
modifies DNA and makes it less likely to be expressed.
Poor maternal care induces methylation of a stress-response gene, causing a lifelong heightened response to stress.
what does methyl group do?
act as a blockade
Basics of Epigenetics
nucleotide sequence is
a method for changing
levels of gene transcription
Epigenetic Effects on Mouse Behaviour
In rat with maternal care:
GR gene normally methylated.
High levels of maternal care remove methylation.
Increased expression of GR mRNA.
In rat with no maternal care:
Cort binds to GR to shut down Cort release.
Decreased GR, more Cort release = highly stress reactive-- dont explore plus maze
Epigenetics and Depression
CpG methylation of GR promoter in patients that committed suicide.
Recall: 95% of depressed patients complain of stress before symptoms began.
Corticosteroid levels are high in depressed patients (suggests lack of feedback inhibition in HPA axis).
Majority of SSRI's (treatment for depression) stabilize HPA axis.
At birth, we have most of the cells we will ever have...but additions to the brain are made in adults.
Adult neurogenesis is the creation of new neurons in the adult brain.
2 regions of the brain continue to show post natal generation of new neurons.
-hippocampus (huamns) and olfactory bulb (not in humans).
-new neurons added to hippocampus daily; ~700 in humans
study with radio carbon dating to reveal new neurons in adults
-Above-surface nuclear bomb tests from 1940s to 1960s released radioactive C14 into the atmosphere.
Test treaty ban in '68; decline in atmospheric carbon.
-Incorporation of 14C into cells; steady background rate in body/brain.
-Levels higher in hippocampus; dividing cells need carbon.
-in new cells more decayed radio carbon was found
are more neurons better?
More is better? No- infantile amnesia.
Too many neruons in the first few years!
functional implications of adult neuronogenesis
Memory formation: adult born neurons are highly excitable; studies support role for addition of new neurons in the formation of memories.
Old neurons die, new ones take their place- plasticity!
How do cells dies as we get older?
Increased cell death-induced via diet or via apoptosis (oxidative damage).
what does memory impariment correlate with?
shrinkage of the hippocampus during aging.
Immediate memory does not decline, while delayed memory does—correlated with hippocampal volume.
Neurogenesis is decreased in Alzheimer's disease.
study: presented with paragraph, pause and then recall the words, what was the outcome?
poor outome= small hippocampus (poor delayed recall)
is a drastic failure of cognitive ability
Alzheimer's disease (AD)
most common form of age-related
dementia, associated with decline in cerebral metabolism
1 million in Canada; 35 Million people world wide.
AD begins as memory loss of recent events; AD brains show reduced metabolism and cortical atrophy.
risk factors for AZ, treamtnet and prevention
Risk factors: Age, family member with the disease, female (two X chrom inc chances of getting AZ), APOE4 gene, head injury, poor diet, etc.
-protective factor: education
Treatment: medications to increase Ach signalling in brain.
Prevention: use it or lose it.
how is AZ characterized?
AD is characterized by senile plaques (beta-amyloid) and neurofibrillary tangles (mainly made of tau).
Neurodegeneration of neurons; hippocampus seems to be most vulnerable—degenerates first.
AD can only be identified via post mortem examination; presence of plaques and tangles
AZ and the proteins involved
β-amyloid buildup (impairs synaptic function) occurs when amyloid precursor protein (APP) is cleaved by two enzymes:
β-secretase and presenilin—> cause formation of beta-amyloid.
Apolipoprotein (ApoE) breaks down β-amyloid.
The second characteristic protein of AZ is Tau, which makes up neurofibrillary tangles. These tangles are directly related to the magnitude of cognitive impairment.
Gene mutations in these proteins are associated with Alzheimer's.
Sensory receptor organs
are organs specialized to detect a certain stimulus.
Receptor organs are very diverse
within the organ convert the stimulus (plural:stimuli) into an electrical signal.
An adequate stimulus is the type of stimulus to which a sensory organ is particularly adapted.
E.g., adequate stim for eye is light energy
Sharks and hunting with sense
use magnetic feilds to navigate, hammerhead has wide navigational feild.
Ampillae of lorenzini put out electrical activity
snakes and hunting
hunt by heat radiation
what do bat detectors do?
hear rats and mices' vocalizations that are too high for the human ear
Sensory systems have a restricted range of responsiveness. Whats an example?
Example: the frequency range for hearing, which varies with species--> cats hear high frequencies humans dont and elephants hear low frequencies humans dont
Gouldian finches can see:
vast wavelengths of light
Bees and some birds can see:
ultravoilt waves emitted by flowers
How do we know what type of stimulus we are perceiving?
Doctrine of specific nerve energies- how does the brain percieve each individual nerve tract's information?
The doctrine of specific nerve energies says:
Receptors and neural channels for different senses are independent.
Each sense uses a different "nerve energy"
Labeled lines: brain perceives different sensory experiences as distinct because each sense modality sends Action potentials via separate nerve tracts.
E.g., hearing—sense organ activates a labeled line that signals sound.
How do we know what type of stimulus we are perceiving? true story: sensory processing
Energy is detected by sensory cells; specialized for certain stimuli.
Energy or chemical is "converted"—sensory transduction.
Sensory transduction—results in local changes in membrane potential; termed receptor potentials (or generator potentials) its excitatory and resembles EPSPs
The Pacinian corpuscle (or lamellated corpuscle) is a skin receptor that detects vibration and pressure.
A stimulus to the corpuscle produces a graded electrical potential.
When the potential is big enough, the receptor reaches threshold and generates an action potential.
Function of Pacinian corpuscle in humans?
Not really known... used to social insects for communication
Six important aspects of sensory processing:
coding, adaptation, pathways, suppression, receptive fields, attention.
is all sensory info processed?
no, Sensory organs and pathways convey limited information—information is processed and some is lost (or actively suppressed).
patterns of action potentials in a sensory system that reflect a stimulus.
The number and frequency (# per given unit of time) convey information that must be interpreted by the CNS.
-How is stimulus intensity encoded?
-Action potentials are "all-or-none" and always the same magnitude.
-Changes in intensity are coded via action potential frequency—> the larger the stimulus, the higher the frequency.
-How is this achieved at the receptor level?
Dynamic Range: range of intensities for which a receptor can encode stimuli.
Cell A: large changes in stimulus causes small change in frequency of action potentials (APs).
-large dynamic range, poor stimulus discrimination.
Cell B (and C): small change in stimulus causes a large change in frequency of APs.
-narrow dynamic range, good stimulus discrimination.
-A single neuron solution to convey stimulus intensity- a change the frequency of its action potentials.
Sensory Information Processing Is Selective and Analytical
Neurons can fire a max of about 1200 APs/second (i.e., lot of capacity to represent the intensity of a stimulus).
Majority of sensory cells do not fire this many (on the order of 200/sec...so they max out at low a low frequency of APs).
Problem: we can detect differences in intensities much greater than this type of encoding can offer.
takes place when different cells have different thresholds for firing, over a range of stimulus intensities.
-groups of receptors work together to increase dynamic range without decreasing sensory discrimination
How is the location of a stimulus encoded?
The somatosensory system detects body sensations, including touch and pain.
Stimulus location is determined from the position of the activated receptors.
E.g., if a receptor on foot is activated, we perceive the stimulus to be there.
There is an orderly map of the sensory systems for vision and touch- map reflects density and position of receptor.
-receptors for hand located in the hand; higher density of receptors in hand compared to back of leg.
-higher density of receptors allows for better discrimination of stimuli abut also increases sensitivity.
only when a stimulus is strong enough there is...
an action potential and you detect it
if its infront off you, reaches the ear at the same time, if its on your left it reaches your left ear first
"Don't overwhelm me"- your brain.
Receptor systems lose the ability to respond to constant stimuli- a form of control.
Adaptation—the progressive loss of response to a maintained stimulus.
Once the stimulus has been detected, we do not need to be constantly reminded that it is there...unless it's really important.
E.g., natural gas is odourless. An additive, mercaptan,gives it a rotten sulphur smell...like a skunk.
When we smell it, it is quite pungent and repulsive...we know it is there.
Repeated stimulation of the receptors in the nose results in a dulling of the scent (even though it is still present in the air).
In terms of adaption, there are 2 kinds of receptors:
show slow or no decline in action potential frequency-show little adaption
In terms of adaption, there are 2 kinds of receptors: Phasic receptors:
display adaptation and decrease frequency of action potentials.
Reason?...we don't want to overwhelm our brains with useless information.
why does adaption happen?
Adaptation allows to attend to novel stimuli more rapidly.
Sensory systems emphasize change in stimuli- more likely to be important for survival.
Adaptation is not the only method- we can quiet receptors by suppressing the stimuli, preventing firing of the receptor.
8 Suppression: Forced Adaptation examples
E.g. 1, via accessory structures, such as eyelids.
E.g. 2, contraction of muscles in inner ear- decreases intensity of sound waves on tympanic membrane.
higher brain centres suppress some sensory inputs and amplify others; e.g., turning down pain at the level of the spinal cord.
The receptive field
-is the space in which a stimulus will alter a neuron's firing rate.
Experiments test what makes a cell change from its resting state- stimulus can be touch, vibration, temperature, pain.
Receptive fields differ in size, shape, and response to types of stimulation.
Response of cell in the brain is determined by receptive field.
Typical Somatosensory Receptive Fields
On centre off surround (touch outside of recetpive feild- no effect it is inhibited, touch centre it excites), off centre on surround
Eye receptor feilds
on centre/ off surround. centre causes action potentials when light hits it, when light hits the surround it inhibits any action potentials from firing, if it hits both they cancel eachother out
sequence of events in recptor feilds in eye
eye--> on centre--> cone---> bipolar cell--> ganglion cell--> visual corte--> stimulation!
Why do we have Receptive Fields?
- better able to see predators or discontinuities (edges) in the objects we feel.
______("fields") in the cortex for a given sense modality (touch, pain, etc):
primary sensory cortex
A separate primary sensory cortex exists for each modality e.g. touch and pain
Secondary sensory cortex
Secondary sensory cortex, or non-primary sensory cortex, receives its main input from the primary cortical area for that modality.
Primary and non-primary share info via cortical loops- secondary recieves info directly from the primary somatosensory cortex for that modality
Primary somatosensory cortex (S1), or somatosensory 1
receives touch information from the opposite side of the body.
Secondary somatosensory cortex (S2),or somatosensory 2
maps both sides of the body in registered overlay- e.g., left and right arms occupy the same part of the map.
Sensory Specialization-star nosed mole
Some animals have a different pattern of representation in somatosensory cortex.
The nose of the star-nosed mole is an organ for touch, and its somato-sensory cortex responds to input from the star-- feelers have adjacent areas of the brain similar to cortical barrel feilds of mice
in the brain show a mixture of inputs from different sensory modalities.
allow for intersensory interactions.
Synesthesia is a condition in which a stimulus in one modality creates a sensation in another.
Examples: a person may perceive colours when looking at letters or a taste when hearing a tone.
May be due to increased connectivity of brain-more axonal connections across cortex in synesthetes that perceive letters in colour.
Touch- our skin contains a large array of "detectors such as:
-Tickle, cold, hot, pain.
-Touch receptors (mechanoreceptors).
Four tactile receptors detect touch: Pacinian Corpuscle
vibration information, receptive feilds are large and vague "quick on an quick off" (fast adpating)
Four tactile receptors detect touch: Meissner's Corpuscle
small and sharp receptive field, detailed, quick on quick off, reason why you dont feel your clothes all day, lie close to the surface of the skin, MOST DETAIL*
Four tactile receptors detect touch: Merkel Discs
small sharp borders, slow adapting, continue to fire and send information to the brain
Four tactile receptors detect touch: Ruffini Corpuscle
stretch receptor, large and vague, nerve fibres innervate collagen fibers
which tactile receptors most important for braille?
The _____ System Carries Somatosensory Information from the Skin to the Brain
The skin can be divided into bands corresponding to the different spinal nerves that carry axons innervating different regions of the body.
A dermatome ("skin" "slice" or "segment") is a strip of skin innervated by a particular spinal root.
Adjacent dermatomes overlap a small amount
why are dermatomes set up this way in humans?
we were once quadrapedal
Neuroplasticity of Cortical Maps:
Receptive fields can be changed by experience.
The cortical map represents the innervation of a body region.
If the nerve to the body region is severed, the cortical area will shrink.
STUDY done with monkey's hands:
stimulate monkeys hands, map the cortical regions in the brain, removed D3-- pasticity-- D3 innervated by D2 and D4 (they have expanded their cortical representation)
STUDY done with monkey's hands: experiment 2
monkeys hand spins disk repeadely with D3 and D2- resulted in increased cortical space in this region of the brain
humans and touch screen study
increased cortical representation of the thumbs compared to those using a device with no touch screen
If your hand was removed what would happen with regards to plasticity?
neurons respond to touch of face and arm...not hand.
Plasticity typically takes between 2-3 months for the somatosensory cortex to reorganize after the loss of a hand
an unpleasant experience associated with tissue damage.
Pain helps us to withdraw from its source, engage in recuperative actions such as sleep inacitivity grroming that create long lasting behaviours to promote recuperation, and to signal others that something is dangerous; "...while unpleasant, pain is our friend." Percieve pain with the Nav 1.7 gene)
Congenital insensitivity to pain
is an inherited syndrome where the person does not experience pain.
How does total analgesia occur and when was the first documented case?
1932: Total analgesia.
Inherited: mutations in
SCN9A—> encodes a
voltage gated sodium
Nav1.7 highly enriched
in nociceptor nerve
Mutation results in lack
of generator potentials.
No sensation of pain.
what effects perception of pain?
Learning, experience, emotion all affect perception of pain.
Makes diagnosing and treating pain difficult—your perception of pain may be different than mine.
Doctor may ask a set of probing questions to get clues about source and treatment of pain.
The McGill Pain Questionnaire describes three aspects of pain:
1) Sensory—discriminative quality (e.g., throbbing, gnawing, shooting)
2) Motivational—affective (emotional) quality (e.g., tiring, sickening, fearful)
3) Cognitive evaluative quality (e.g., no pain, mild, excruciating)
are peripheral receptors that respond to painful stimuli.
Free nerve endings
in the dermis have specialized receptor proteins.
The free nerve endings respond to temperature changes, chemicals, and painful stimuli.
what does inflammation do?
Inflammation functions to 1) prevent further necrosis, (2) provide an environment in which cell debris and pathogens can be disposed of, and (3) activates mechanisms for repair.
Labelled line—detection of heat.
Detection of heat (i.e., increased temperature)- transient receptor potential vanilloid type1 (TRPV1), or vanilloid receptor 1; "am I on fire?"
Capsaicin—the chemical that makes chili peppers "hot".
TRPV1 binds capsaicin..."this food is spicy!".
Pain control- capsaicin cream--> receptors for pain turn off after capsacin cream
The TRP2 receptor differs from TRPV1:
Detects even higher temperatures than TRPV1 (a receptor found in some free nerve endings that opens its channel in response to rising temperatures).
TRP2 Does not respond to capsaicin.
Is found on Aδ fibres—large myelinated axons that register pain quickly; needed to activate reflex if you burn yourself.
TRPV1 receptors are on C fibres—thin unmyelinated axons that conduct slowly, producing lasting pain.
They are responsible for dull pain
cool-menthol receptor 1 (CMR1)
The cool-menthol receptor 1 (CMR1) responds to menthol and to cool temperatures—located on C fibers. Rather slow.
A delta fibre respond to....
The anterolateral, or spinothalamic, system
transmits the sensations of pain and temperature.
Free nerve endings synapse on spinal neurons in the dorsal horn.
Pain information crosses the midline in the spinal cord, before ascending to the thalamus.
important for shutting down pain
Peripheral fibres probably use glutamate to excite cells in the dorsal horn of the spinal cord.
They also release substance P, a neuropeptide.
Postsynaptic neurons take up substance P and remodel dendrites (become varicose), which may affect pain perception (sensitization?).
recruits maast cells, releases histamine- dialte blood vessels so more blood enters site
when there is trauma to a site what is released?
seratoin, potassium, prostoglandins, Leukotrienes
controls hormone secretions
reproductive maturation, body rhythms
pituitary gland: anterior pituitary:
hormone secretion by thyroid, adrenal cortex and gonads
also responsible for growth
pituitary gland: posterior petuitary
water balance, salt balance
growth and development, metabolic rate
Adrenal glands: Adrenal cortex- outer bark
salt and carbohydrate metabolism, inflammatory reactions
Adrenal glands: adrenal medulla
digestion and appetite control
gonads (testes/ ovaries)
body development, maintenance of reproductive organs in adults
Endocrine feedback loops
endocrine gland releases hormone that acts on target and feeds back in autocrine fashion to inhibit further hormone secretion
-hormone from endocrine gland acts on target cell to produce biological effects and consequences of these effects may be detected by endocrine gland causing further inhibition
-Brain may become involved- e.g. hypothalamic region drives endocrine gland via either neural or hormonal signals. Target organs signals brain to inhibit this drive
-feedback is regulated by mutliple routes
secretions of the anterior pituitary
hormones produced in the anterior petuitary include tropic hormones, which control endocrine glands and directly affect other structures, such as bones
secretions of the anterior pituitary: CRH and its effects
CRH (corticotropin releasing hormone)
this tropic hormone affected ACTH, ACTH's main target is the adrenal cortex, and the corticosteriods hormones are released
secretions of the anterior pituitary: TRH releasing hormone
affects TSH--> thyroid--> thyroid hormones
secretions of the anterior pituitary: GnRH (stimulates) and GNiH (inhibits)
affects LH and FSH--> testes and ovaries--> androgens and estrogens, porestins
secretions of the anterior pituitary: Prolactin releasing peptide and Prolactin inhibiting factor
affects prolactin--> mamillary glands for milk production
secretions of the anterior pituitary: somatocrinin (Stimulates) and somatostatin (inhibits)
affets GH--> bones growth
contols production of release of hormones in adrenal cortex
inc release of hormones from thyroid gladn
stimulates growth and maturation of egg-containing follicles and the secretions of estrogens within the follicles in the ovaries
-in males responsible for sperm production
causes ovaries to release eggs, in males causes testes to produce testosterone
promotes lactation in female mammals
Synopsis of releasing hormone
some hormones are controlled by releasing hormone from the hypothalamus that regulates the release an anterior petuitary tropic hormone whichin turn controls the secretion by an endocrine gland. The endocrine gland then performs neg feedback to hypothalamus and petuitary
Explanation of posterior petuitary hormones
they are manufactured by neuroendocrine cells in the hypothalamus wheich send their axons down to the petuitary stalk,ti terminate on capilaries there. when these neuroendocrine cells are stimulated to produce an action potential they release oxytocin or vassopressin into circulation
Explanation of HPG Axis
hypothalamic cells secrete GnRH into the hypophyseal portal system to stimulate anterior petuitary cells to release FSH, and LH which stimulate the gonads to release steriod hormones. The principle gonad steroids in males are androgens such as testosterone , while the ovaries release estrogens such as estradiol and progestrins such as progesterone
Negative feedbalk loop
monitors and controls secretion of hormones. The hormone acts on target cells, leading them to change the amount of a substance that they release. In the simplest case the hormone also acts on the endocrine cell and regulates further output by endocrine gland. In more complex case, target cells release substance that in turn regulates output of endocrine gland
Anterior petuitary and hypothalamus interaction
anterior petuitary hormones are controlled by the overlying hypothalamus. /hypothalamic neuroendocrine cells send axons to the median eminence to secrete releasing hormones to the petuitary. Dif hypothalamic releasing hormones either stimulate or inhibit anterior petuitary cells that secrete tropic hormones
Phantom Limb Pain is an example of neuropathic pain (pain caused by damage to peripheral nerves)
Continued perception of pain long after the initial stimulus has passed can be problematic.
Neuropathic pain may be due to inappropriate signalling of pain by neurons.
Dorsal horn neurons can become hyperexcitable and cause chronic pain.
May be due to neuroplastic changes induced by the initial pain stimulus ("neurons that fire together...").
Microglia Mediated Hyper-excitability: phantom limb
After peripheral nerve injury like a lost limb, -microglia surround the synapses between pain fibers and neurons in the dorsal horn of the spinal chord. The microglial cells release chemicals that make the dorsal horn neurons hyperexcitable. Nearby astrocytes also boost the effectiveness of the synapses between pain fibres and spinal cells. The dorsal horn neurons become chronically active flooding the thalamus with action potentials signalling pain.
Phantom limb sensation:
sensation in a limb that has been amputated; experienced by virtually all amputees.
Not necessarily painful—>e.g., itchy finger on a hand that is no longer there
Phantom limb pain:
pain in a limb that has been removed; not the same as "stump" pain.
what mechanisms contribute to phantom limb?
Several mechanisms likely contribute: begins in periphery with activation of nociceptors, increases plasticity in dorsal horn and spreads to cortex.
-individuals with a phantom limb sense that limb "retracts", such that it is shorter than the amputated portion of the arm. This is reported to be painful, as it "feels" like the arm is contorted in an unnatural fashion.
Cingulate cortex and pain
amount of pain felt correlates with degree of activation of cingulate.
Involved in emotional, cognitive, and motor tasks
experiencing and empathizing with pain and activated brain regions
Different subregions of the cingulate cortex are activated if a person is experiencing (both anterior and posterior) the pain or is empathizing (only the anterior) with another.
the loss of pain sensation
are drugs that control pain.
are endogenous opiate-like peptides in the brain.
Three classes of endogenous opioids :
are endorphins, enkephalins and dynorphins.
G-protein coupled receptors (GPCR's)
Opioid receptors respond to opiates or opioids; mu, kappa, and delta.
Results in hyperpolarization- how?
Opiods bind to K channel, stops action potential from occuring-- hyperpolarization
The periaqueductal gray (PAG)-what happens when stimulated?
midbrain region involved in pain perception; stimulation of the PAG produces potent analgesia.
Pain information can be blocked by a "gating action" in the spinal cord.
LOOK up ascending and descending pain pathways
How does marajuana work to stimulate endogenous receptors?
Marijuana can be an analgesic and works by stimulating endogenous cannabinoid receptors (CB1 receptors) in the spinal cord and in the free nerve endings of the nociceptors-- so its possible to devise topical creams through the skin to relieve painTW
types of pain intervention: placebo
may activate endorphin-mediated pain control system
but ethical concerns about decieving pateint
types of pain intervention: accupuncture
seems similar to TENS or placebo, sometimes affected by opiate antagonists-- activates endogenous opiods (Administering nalaxone reduces pain relief effects)
what are steriod hormones derived from?
hormone only found in males?
platypus uses what for hunting?
bill- used for touch
faulty metabolism of amino acid
what is not highly represented in sensory homonculous?
describe biological value of info supression and ways supression is achieved by nervous system?
so we dont overwhelm the brain, focus on other things that might be essential for survival. Achieve this by accessory systems- like closing eyelids and thightening muslces in ear, descending pain pathway etc
Protein hormone action steps
protein hormone receptors are found in the cell membrane, when the hormone binds to the receptor, a second messenger system is activated, which affects various cellular processes
steriod hormone action steps
steroid hormones diffuse passively into cells. inside the target cells are large recptor molecules that bind to the steroid hormones. The steroid receptor complexes then bind to DNA, causing an increase in the production of others. This is the mechanism by which steroids exert a genomic effect.
Single nucleotide polymorhpisms (SNPS)
Minor variations where one nucleotide substitutes another- can occur at certain locations on a gene
-many have two different version or alleles
-cause variation within traits such as eye colour, susceptibility to disease etc.
-advantageous genes will be under selective pressure and passed on to future generations
the outer cellular layer of the developing fetus, giving rise to the skin and nervous system (during development it leads to the neural plate)
in the developing embryo, the groove between the neural folds, progresses into neural tube, becomes the midline
embryonic structure with subdivisions that correspond to the future forebrain, midbrain, hindbrain, central canal of spinal chord, and passages that connect them at 22 days can see the brain at the anterior end
anterior division of the brain, containing the cerebral hemispheres, the thalamus, and hypothalamus
middle division of brain
rear division of brain, mature vertebrate contains the cerebellum pons and medulla
earliest stage in developing animal
a region lining the cerebral ventricles that displays mitosis, providing neurons early in development and glial cells though out life
Explanation of 6 step process of neural development
cells of the neural tube divide to provide progeny cells, the cells produced migrate to their appropriate regions, each cell differentiates to become a particular type of neuron or glial cell, neurons extend their axons and dendrites and form many synapses with one another, many neurons normally die early in development, many of the synapses initially formed... will be later retracted... while other, later appearing synapses will form.
Radial glial cells
during cell migration, cells dont move in a haphazard pattern
-move along a particular type of glial cell called the radial glial cells which extend from the inner to outer surfaces of the nervous system
-newly formed cells creep along them
destruction of the nerve cell body following injury to its axon
also called Wallerian degeneration. The loss of the distal portion of an axon resulting from injury to the axon
-this may regrow, CAMS help guide regenerating axons
Axons and dendrites of young neurons and their growth
extreme growth of axons and dendrites in their early life (called oprocess outgowth) and the proliferation of synapses (called snyapotgensis). At tips of axons and dendrietes, specialized swellings called growth cones are found. Filipodia extend from the growth cone, they adhere to CAMS and then contract to pull the growth cone in a particular direction
fragile X syndrome
a condition that is a frequent cause of inherited intellectual disability. Produced by fragile site on the X chromosome that seems prone to breaking because the DNA there is unstable. More common in males than females. Have elongation of the face, prominent ears, prominent chin, mild to severe cognitive impairment
-underlying cause: trinucleotide repeats; repetition of the same three nucleotides within a gene- most normal people have 6-50 but if more than 200 are inheited they will get fragile X syndrome
Hypothesis on how AZ develops
-an extracellular portion of the amyloid precursor protein (APP) is removed by B secretase; then an intracellular portion is cleaved by presenilin, relasing B amyloid extracellularly
- B amyloid clumps together, forming extracellular plaques, some of which accumulate on axons and dendrites, impairing synaptic function
-B amyloid also accumulates inside neurons which respond by forming neurofibillary tangles filled with Tau protein
-Basal forebrain neurons, in response to the neurotoxicity of amyloid plaques and neurofibillary tangles, cease producing achetocholine leading to dementia
-APoE may normally break down beta amyloid ppreventing formation of plaques. People with one or two copies of the ApoE4 version of the gene seem to build up plaques faster
mechanical stimulation of corpuscle and when threshold is reach-- Action portential (steps involvled)
1) mechanical stimulation deforms corpuscle
2) deformation of corpuscle stretches the tip of the axon
3) stretching the axon opens mechanically gated ion channels in the membrane allowing sodium ions to enter
4) when receptor potential reaches treshold amplitude the axon produces one or more action potentials
For most senses where does the information go to first before reaching the cortex?
the thalamus-- the thalamus may emphasize some stimuli while supressing other information-- top down processing
epidermis, dermis and hypodermis
epidermis: outermost layer of skin
dermis: middle layer
hypodermis: also called subcutaneous tissue, innermost layer of skin under the dermis
Peripheral mediation of pain
damaged cells release substances that excite free nerve endings that function as nociceptors, action potentials generated in the periphery can reflexively excite blood vessels and other cells to produce information, information enters through the dorsal root and synapses on neurons in the dorsal horn, pain fibres release glutamate as a transmitter and substance P as a neuromodulator in the spinal chord. Then the dorsal horn cells send information accross the midline and up to the thalamus
Gastrin releasing peptide (GRP)
a neuropeptide that stimulates neurons in the dorsal horn to provide the sensation of itch
(free nerve endings provide us with the sensation of itch, responds to histamine released from mast cells in the skin- send their slowly conducting c fibres to spinal chord where they use GRP
Pain ascends the spinothalamic system to reach the brain
pain information carried by rapidly conducting mylentated A delta fibres and slowly conducting unmylenated C fibres, axons of dorsal horn neurons cross the midline and ascend the spinal chord in the anterolateral quadrant, pain information is provided to various brainstem sites which control pain related behaviour such as vocalization, pain information is distributed to many thalamic and cortical areas, cingulate cortex is especially activated by pain information
What effects does chronic pain have on the brain?
gray matter in dorsolateral prefrontal cortex of people with chronic back pain shrinks faster than normal aging
treating of phantom limb
patient pecieves missing limb is twisted or clenched
-pateient looks at himself in a mirror positioned in such a way that the reflection of the intact limb seems to have filled in for the missing limb. Patient moves " both limbs" and reports that it no longer hurts
Ascending and descending pain pathways
brainstem controls pain transmission in the spinal cord. Periaquedal gray neurons send endorphin containing axons to stimulate neurons in medulla. These medullary neurons send axons to the spinal chord, eventually stimulating neurons to release opiods there. Pain information is blocked by direct gating action in the spinal cord.
Electrical stimulation of the descending tract inhibits the response of spinal cord sensory relay cells to noxious stimulation of the skin. Morphine provides analgesia by stimulating the opiod receptors in this descending pain control system, in both the brainstem and the spinal cord.
delivery of electrical pulses through electrodes attached to the skin which excites nerves that supply the region to which the pain is referred. We know TENS acts at least in part by releasing endogenous opiods because the administration of nalaxone (opiod antagonist) blocks this analgesic action.
stressful situations and pain relief
pain inhibition arises in stressful circumstances, brain systems produce analgesia when pain threatens to overwhelm effective coping strategies
classes of steroid hormones produced in the adrenal cortex:
Glutocorticoids- Hydrocortisone (cortisol)
This hormone helps control the body's use of fats, proteins, and carbohydrate
This hormone regulates the level of sodium excreted into the urine, maintaining blood volume and blood pressure.
Androgenic steroids (androgen hormones) eg androstenedione
These hormones have a small effect on the development of male characteristics.
Epinephrine (Also called adrenaline.)
This hormone helps the body respond to a stressful situation by increasing the heart rate and force of heart contractions, facilitates blood flow to the muscles and brain, causes relaxation of smooth muscles, helps with conversion of glycogen to glucose in the liver, and other activities.
Norepinephrine (Also called noradrenaline.)
This hormone has little effect on smooth muscle, metabolic processes, and cardiac output, but has strong vasoconstrictive effects, thus increasing blood pressure
Pain control- opiod agonist G protein activation
opiods bind to cell, opens K channel, stops action potential from occuring, hyperpolarization
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