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4/28 - Lectures 19, 20, 21
Terms in this set (129)
T/F: The hypothalamus is the master regulator (mediator) of homeostasis.
True - dur.
Homeostasis - maintaining a constant state...
What three major components does the hypothalamus regulate?
T/F: Massive lesions of the hypothalamus are not compatible with life.
From what external areas does the hypothalamus get information?
What things can the hypothalamus sense via its interoreceptive neurons?
circumventricular organs - areas of brain with no blood-brain barrier - include areas in the hypothalamus so that the hypothalamus can sense changing hormone, etc levels and then have projections back to the hypothalamus
What kind of homeostatic setpoints does the hypothalamus maintain? What nucleus maintains circadian signals?
circadian signals - suprachiasmatic nucleus
outputs to the amygdala are important in mediating responses to threats/attacks
Critical in reproductive behavior and hormones of reproduction
T/F: The hypothalamus has direct connections to the autonomic control neurons
T/F: The hypothalamus has both direct and indirect connections to regulate both the anterior and posterior pituitaries.
T/F: There are collections of neurons in the hypothalamus that have broad, diffuse projections to the entire neuraxis
True - there are neurons that innervate the cerebral cortex directly, the thalamus, spinal cord, etc - several of these are key regulators of behavioral control
T/F: There is direct innervation from the eye to the suprachiasmatic nucleus
Describe the retino-hypothalamic pathway
True - monosynaptic input - thus SCN is directly affected by light
Recall, this pathway was described in the visual lecture:
retina -> suprachiasmtic nucleus -> paraventricular hypothalamic neurons -> intermediolateral cell column -> superior cervical ganglion -> pineal gland -> pineal gland releases melatonin
The hypothalamus sits at the base of the skull - what bony structure forms the border for this pituitary gland?
The rostral boundary of the hypothalamus is the _______ and the caudal boundary is the ________.
optic chiasm; mamillary body
What happened in Frohlich's syndrome? What symptoms did they present with?
pituitary tumors arising from the anterior lobe
presented with the following symptoms: obesity, derangement of every endocrine axis, hyperphagia (increased hunger)
As the tumor enlarged, it moved up and affected the hypothalamus (current studies show that if you damage the hypothalamus you get the same symptoms)
What are the three broad classes of hypothalamic neurons?
magnocellular, parvicellular hpophyseotropic neuron, hypothalamic projection neurons
What kind of neurons make Vasopressin (ADH) and Oxytocin? Where are they released?
these are released by posterior pituitary (neural lobe - collection of axon terminals from these neurons as well as support cells)
oxy - milk letdown, myometrial contractions during birth
ADH - fluid balance, blood pressure
released into general circulation
Which neurons release "releasing factors" at the level of the median eminence? From which pituitary gland are these factors ultimately released?
The parvicellular hypophyseotropic neurons (he has continually said to not worry about nomenclature)
The median eminence is made up of the pituitary portal vessels - "releasing factors" go into the portal vessels and bathe the anterior pituitary gland - the anterior pituitary gland then releases its own hormones
Thus this is an INDIRECT form of regulation of anterior pituitary gland function by these neurons
What do projection neurons regulate?
do not regulate endocrine function, but regulate other parts of the brain - autonomic system and behavior
Mini-review: The magnocellular neurons project to where?
The posterior pituitary lobe is just the axon terminals of the magnocellular neurons in a big vascular plexus
Mini-review: The parvocellular neurosecretory cells release their "releasing factors" where? What lobe does this affect?
Release them at the hypophyseal portal system at anterior pituitary lobe -> causes release of anterior pituitary hormones
indirect regulatory system
For a while, people thought that the direction of flow of signals was from the pituitary glands back up to the hypothalamus.
Thanks Geoffrey Harris and some other dudes (Guillemin and Schally - discovery of "releasing factors") for figuring out what really happens.
He talked about history a lot...
Describe the function of each releasing hormone:
TRH -> increase TSH and thyroid activity
CRH -> corticotropes -> release ACTH -> control stress axis
GHRH - growth-hormone releasing hormone -> act on somatotropes -> release GH (somatostatin inhibits GH)
dopamine -> key regulator (inhibitor) of prolactin secretion from anterior pituitary
GnRH -> responsible for release of LH & FSH from anterior pit
CRH and TRH-immunoreactive terminals are found in which zone of the hypothalamus?
AVP-Immunoreactive terminals arising from _________ neurons are found in which zone of the hypothalamus?
Releasing factors are released into what structure of the hypothalamus?
the median eminence, shown on the bottom right
Each nuclei releases different factors
He doesn't seem to want us to memorize all of the nuclei - but it might be helpful conceptually to know that the PVH does release releasing factors into the ME (median eminence)
SON = supraoptic nucleus
PVH = paraventricular nucleus of hypothalamus
T/F: There are direct monosynaptic connections from the hypothalamus to autonomic control neurons.
The preganglionic parasympathetics are mainly located in the ________ and the ______ _____. For the viscera the dorsal nucleus of the vagus is a well-known example.
The preganglionic sympathetics are located mainly in the ______________ ________ _______.
brainstem; CN nuclei; intermediolateral cell column (exists at levels T1-L2.
There are very few places that innervate the IML - the few that do innervate must have powerful regulatory outflow.
What is an example?
If you stimulate the lateral hypothalamic area you can cause profound changes in blood pressure and heart rate.
Leptin regulates sympathetic outflow as it relates to energy expenditure. There are hypothalamic neurons that respond to leptin and directly project to the sympathetic column. When you lack leptin, _______ consumption and body ________ are low. If you give leptin back, you can correct that.
Believed that direct connection to the hypothalamus underlies this phenomenon.
How might the hypothalamus regulate arousal?
There are neurons in the posterior hypothalamus that make histamine - the only source of histamine in the mammalian brain - but the entire brain gets histaminergic innervation. So the neurons in the hypothalamus making histamine innervate the entire neuraxis.
Histamine is key for arousal - thus these neurons are key in regulating arousal.
The MCH hormone released by the hypothalamus has been shown to be an important regulator of what?
What area of the hypothalamus makes orexin?
The lateral hypothalamic area
orexin and hypocretin is the same thing
To where do neurons releasing orexin have projections?
to the entire brain and spinal cord - to the entire neuraxis (except perhaps cerebellum)
What does orexin deficiency cause?
narcolepsy - specifically, the orexin 2 receptor
CSF taps from patients experiencing narcolepsy showed what?
a total lack of orexin, neurons are "killed" (totally gone) even though neurons just adjacent (such as MCH) are totally intact.
Via what mechanism are orexin neurons destroyed?
What is narcolepsy characterized by?
1) not going through the normal paths of sleep - slow wave to REM, etc - total amount of sleep is not different, but there is total disorder
2) behavioral arrest and atonia (no voluntary muscle contraction)
In narcolepsy, you go straight from wake to what sleep cycle?
REM - atonic and unable to move
Orexin deficiency's biggest signature (at least in the mouse model) is what?
Cataplexy - a sudden and transient episode of muscle weakness accompanied by full conscious awareness, typically triggered by emotions such as laughing, crying, terror, etc
In sum: A patient presents to you with an episode of cataplexy - what is the likely diagnosis? What is the likely biochemical mechanism?
narcolepsy; orexin deficiency
Why not just give orexin?
because the blood-brain barrier won't allow crossing, and also it's uncertain what other effects giving generalized orexin would have on the autonomic function, etc
BEGIN LECTURE II MATERIAL
What does the current understanding of the limbic system include?
What are cortical components of the limbic system?
What are the non-cortical components of the limbic system?
What are the various components of the limbic system (which gyri, cortexes, etc)?
Where is the cingulate gyrus?
Recall that the cingulate gyrus is continuous with the temporal lobe via the isthmus
Where is the isthmus?
Where is the parahippocampal gyrus and the uncus?
Where is the subcallosal area?
Where is the olfactory tubercle and the pyriform cortex, respectively?
The pyriform cortex is really part of the parahippocampal gyrus
What components of the hippocampus are involved in the limbic system?
pyramidal cell layer
subiculum (or subicular cortex)
Where are the dentate gyrus, pyramidal cell layer, and subiculum within the hippocampus?
CA1-CA4 are parts of the pyramidal cell layer
Major input to the hippocampus comes from where?
parahippocampal gyrus - specifically, the enorhinal cortex
Major output from the hippocampus goes to where?
additional input to amygdala
What is the pathway for input into the hippocampus?
To where does output from the hippocampus go? Output travels via axons in what structure? A majority of the output originates from where?
Quick review: The hippocampus sends projections to which areas? Via what structure?
Also sends to amygdala and other limbic structures - with amygdala there is feedback
What is the last of the limbic components?
Which areas make up the prefrontal cortex?
Where does the prefrontal cortex receive input from?
Output from the prefrontal cortex goes mainly to where?
ventral striatum (ventral portion of the caudate putamen)
The prefrontal cortex is part of the "association" cortex. What do its domains include?
The amygdala receive input from where?
-all sensory systems
-Hippocampus (and other limbic areas)
To where does the amygdala send projections?
emotional responses can cause autonomic activation
limbic cortex - especially the prefrontal cortex
Quick review: To where does the amygdala send projections? Via what pathways does it send projections? From where does it receive projections?
The septal area receive input from which two areas? It gives major output to which areas? The septal area is a major source of limbic system influences on ________ responses.
Pathway: medial forebrain bundle
Quick Review: The septal area receives input from which two areas? Via what pathway? It sends output to where? Via what pathway?
Another pathway between the amygdala and the septal area is the ventral amygdalofugal pathway
The septal area is a major source of limbic system influences on visceral responses - communicated via medial forebrain bundle
Which areas of the ventral basal ganglia contribute to the limbic system?
ventral striatum - very ventral portion of the caudate and putamen
ventral pallidum - analogous to the globus pallidus
From where do the ventral basal ganglia receive major input from? Most projections are sent to where?
receives dopaminergic input - ventral tegmental area is analogous to the pars compacta of substantia nigra
sends projections to dorsomedial thalamus -> dorsomedial thalamus influences prefrontal cortex
What do the ventral basal ganglia have influences on?
Describe the limbic loop from cortical input to thalamus
Which thalamic nuclei make up the limbic thalamus?
anterior and dorsomedial nuclei
From where does the limbic thalamus receive input?
To where does the limbic thalamus send output?
What are the functional domains of the limbic thalamus?
memory - Papez circuit
What are the limbic regions of the hypothalamus? The input to the hypothalamus comes from where? Output goes to where?
Hypothalamus plays a central role in what?
What are the pathways to and from the hippocampus called?
The median forebrain bundle connects what structures?
What do the stria terminalis and ventral amygdalofugal pathways communicate, respectively?
Recall: Where is the fornix located?
What are the two divisions of the fornix?
The post-commisural and pre-commisural divisions - pre-commisural carries projections from hippocampus to septal areas
Behold! The Limbic System!
What are the functional domains of the limbic system?
explicit (declarative) memory & behavior, emotions, and survival
What is the central limbic system component in the declarative memory domain? Input comes from where? Output goes to where?
What is the primary limbic circuit dedicated to explicit memory?
Do you need more than the hippocampus to have episodic or declarative memory?
output to diencephalon as well as some to the septal area
The major source of information into the hippocampus from the _________ pathway is the __________ cortex in the parahippocampal gyrus. The intial contact is made in the _______ _______.
pyramidal neurons in blue, dentate gyrus neurons in green
perforant; entorhinal; dentate gyrus
On what kind of cell is the initial contact made in the dentate gyrus? From there where does it go?
entorhinal cortex -> dentate gyrus -> synapse at granule cell -> granule cell communicates via mossy fiber to pyramidal cell in the CA3 region of the hippocampus
What does the pyramidal cell in the CA3 area then communicate with? Via what axonal process?
CA3 communicates to CA1
axonal process = Schaffer collateral
Most CA1 pyramidal cells project to neurons where? Others send axons where?
Axons from the subiculum project to where? These are the main source of hippocampal output. Where will the output go?
Output will go to the septal areas and the mamillary bodies
Now it's time to go on a journey...the journey of Papez circuit.
Papez circuit: The fornix sends most of its projections to where? Via what pathway?
the mamillary bodies via the post-commissural pathway - there will also be some direct projections that will stop off and influence the anterior thalamic nucleus directly
Papez circuit: Pre-commisural division of the fornix goes in front of the anterior commisure and influences the ______ area.
Papez circuit: The mamillary bodies will then send projections via a structure called the ____________ tract up to the ________, specifically the ________ _________ nucleus, where they, along with direct projections from ___________ will influence anterior thalamic activity.
How does the hippocampus have both direct and indirect input to the anterior thalamic nucleus?
mammalothalamic; thalamus; anterior thalamic nucleus; hippocampus
the mamillary bodies send a lot of projections to the anterior thalamic nucleus, so the hippocampus has both indirect and direct input to the anterior thalamic nucleus.
Papez circuit: The anterior thalamic nucleus will then send thalamo-cortical projections mainly to the __________ ________.
Axons from the cingulum loop around the curve to end up where? They will influence neurons in the _________ ________.
the parahippocampal gyrus; entorhinal cortex
T/F: Of all the components of the limbic system, damage to the hippocampus will result in the worst memory deficit.
True - memory is complicated and not all components contribute equally - there are some components outside of this system that are also important for memory
Sensory input as well as memories play an important part in our emotional response.
It's true. Just sayin'.
The central player in our emotional circuitry appears to be the _______. An emotional reaction typically includes what three components?
Remember, input from the amygdala comes from which sources?
The output goes to where?
From where does the Amygdala receive input? Where does it send output, and via which specific pathways?
There will be no direct questions about clinical manifestations of these disorders...
Here they are in case you feel that this course does not cover enough material and you'd like to further torture yourself.
CA1 neurons in the hippocampus are very very sensitive to _______ injury.
ischemic - cardiac arrest can result in a severe problem with episodic memory and an ability to form new memories
Photos of damage...
H.M had a bilateral medial temporal lobectomy - could not form new memories
What is Korsakoff amnesic state?
Just putting it here for completeness...
What is Kluver-Bucy syndrome? Results from ablation of the amygdalae - what would you expect that to result in? Similar syndromes described in humans with damage to what?
resulted in monkeys having little concept of social boundaries - those without their amygdala didn't respect social boundaries and were attacked and often killed :(
Pre-frontal lobotomies, Dr. Freeman...bad news for those suffering from mental health issues from the 1940s-1950s.
BEGIN LECTURE III MATERIAL
omg i'm tired.
He said that if you know these learning objectives you will be golden for the test.
What two things are needed for consciousness? What
ARAS - arousal
Bilateral Cerebral hemispheres and thalamus - intellectual and emotional content
What anatomic features do you need for consciousness? Thus, coma will result when one of these is dysfunctional.
Fidelity of what other systems is needed?
ARAS, thalamus, cerebral hemispheres
What five major factors define coma?
Must know these for exam
What are the three components of the Glascow scale?
Eyes, motor, verbal
What is the lowest and the highest Glascow score? How are severe, moderate, and mild scored?
High = 15
Low = 3
What are some of the major causes of coma?
What do the ABC's refer to?
From top to bottom this chart shows order of things you should do in response to a patient
ABCs - what order of things do you do?
For the neurologic assessment, what are some of the most important reflexes to check for?
pupillary light reflex -> Corneal reflex -> caloric tests/VOR -> respiratory pattern
Pupil size is a tug-of-war between what two systems?
Tonic dilation denotes what system? What about tonic contraction?
parasympathetic and sympathetic - I'm not reviewing details here because he glossed over and we've already learned the mechanisms...
Describe what each of the following terms refers to:
Diencephalic pupils - caused by opiate use, could have kidney/liver failure - only constricts a little
Uncal pupils - one eye has no reaction to the light - implies that there is something pushing down on the brainstem - pushing down on parasympathetic nerve (CN III)
Pinpoint pupils - lesion in the pons (could be massive bleed in pons)
midposition pupils - problem in midbrain - shine light and there is NO reaction
Uncal herniation pushes down on the midbrain - what are clinical signs?
causes pupil to dilate (compression of CN II) and causes weakness (compression of corticospinal tract)
When the cause of the coma is toxic-metabolic, is the outcome generally good or bad? What about if it's due to cerebrovascular complication?
Patients who remain in coma for two weeks will often enter what state? They may regain which brainstem functions?
What was the purpose of the Harvard criteria?
To define irreversible coma as a new criterion for death - results of NIH study provided support for this criteria
President's Commission for the Study of Ethical Problems in Medicine and Biomedical Research adopted the Harvard criteria
Prerequisites for brain death
Must know these for exam
These are all things that you have to make sure are NOT happening, because all of these things can cause brain death or its appearance
If patient is hypothermic, that can cause the appearance of brain death - so have to make sure they are NOT hypothermic
What three criteria must be met in order for brain death to be diagnosed in the United States?
Must know these for exam
Apnea = lack of breathing
pharyngeal & tracheal reflexes = cough reflex
Confirmatory testing not required in the United States
As a reminder...more CN exam illustrations...
If the patient has a dark eye color and it's hard to see the pupil, you can use this nifty tool...
Where on the eye do you need to touch in order to cause the corneal reflex?
NOT the white space
As if you could forget after Dr. Frohman's lectures...what does the Cold Caloric test measure? Do you test both sides, or one? You are inserting cold water into which structure? What will happen with a brain dead patient? What about with a patient in coma but not brain dead?
water in and around the semicircular canals...
In a brain dead patient, there will be no response at all.
With coma but no brain death, get slow phase to side of injection, but no fast movement back (no fast movement because you need cerebral hemispheres for saccades)
For the tracheal reflex, you want to get the tubing down to what point?
to the carina
Last part of the exam is the apnea test. How is this accomplished?
Testing base of medulla - respiratory center
Patient is taken off ventilator, given oxygen (you don't need lungs for oxygenation - that's more for ventilation and CO2 movement)
The most noxious stimulus for spontaneous respiration is rising CO2 levels - as CO2 rises to above 60, the patient should breathe spontaneously if that function is still intact
If brain death cannot be defined for any variety of reasons, a confirmatory test must be performed. There are four - what are they?
All of these confirm brain death (these are only needed about 10% of the time - in the other 90% of cases, you can confirm via Coma criteria, Brain Stem reflexes, Apnea test):
Cerebral Angiogram - inject contrast - in brain death, there is so much pressure in the brain, the brain is swelling, the contrast can't get in - called an empty skull phenomenon (shows that no blood is getting to the brain)
Electroencephalogram (EEG) - electrodes placed on the brain - may be cardiac artifacts, but besides that, flat line
Nuclear Perfusion Imaging with Technetium - radiotracer injected into blood - tracer can't make it into the brain, too much pressure - means blood isn't getting to brain (same principle as cerebral angiogram)
Transcranial Doppler Ultrasound (TCD) - ultrasound of the brain - shows that blood is flowing to the edge of the brain but is pushed back quickly
Again, if you know this slide, you will be golden.
THIS SET IS OFTEN IN FOLDERS WITH...
4/14 - Lectures 1, 2, 3
4/15 - Lecture 4, 5, 6
4/18 - Lecture 10, 11
4/21 - Lectures 12, 13
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