A change in behavior based on experience (also called the acquisition of memory), Both learning and memory are critical for survival
What is Learning?
The brain's ability to store & retrieve learned effects of experience, both learning & memory are critical for survival
What is Memory?
Complications/problems with surgeries-learned things when they went wrong & natural experiments of aging & disease, animal studies were needed to look at mechanisms
What was initial understanding of memory based on?
Memories that are made into long term memory from short term memory need time for changes to occur in the nervous system
Why aren't long-term memories made instantly?
The changing of the nervous system-the strengthening or weakening of synapses
What is Consolidation?
That consolidation occurs when a short term memory is stored by paired neural activity (two neurons continuously send messages to each other-strengthens)
What did Hebb suggest?
Effectiveness of a synapse is increased by activity of a presynaptic neuron paired with the depolarization of a postsynaptic neuron, this paired activity eventually produces long-term structural changes in synapses (this would explain why it takes time for consolidation to occur)
How is the effectiveness of a Synapse increased?
Sea slug/sea hare, invertebrate (don't have spinal cord), studied by Kandel, aplysia have a very simple nervous system-only about 20,000 neurons, neurons located in discrete & accessible regions called ganglia (groups of neurons called ganglia)
What are Aplysia and who studied them?
§ The gill & siphon withdrawal reflex of aplysia. A light touch to the siphon with a paintbrush causes the siphon to contract and the gill to withdraw under the protection of the mantle shelf, here shown retracted for a better view
What is the Withdrawal Reflex in Aplysia?
Learned inhibition--> responses are going to decrease with experience (touch it with a paintbrush so many times that the withdrawal reflex decreases--happens because it releases less of the neurotransmitter gluatamate)
What is Habituation?
Touching the tail elicits a tail withdrawal & gently touching the siphon (used to expel seawater & waste) elicits a withdrawal reflex of the siphon & gill
What are the two types of Withdrawal Reflexes in Aplysia?
Siphon (thing you touch) stimulated--> sensory neuron--> excitatory interneuron--> motor neuron--> gill (thing that goes in), presynaptically-recording from the sensory neuron, if you stimulate it--get a large EPSP in the motor neuron; after habituation, get a lower response in the motor neuron; sensory neuron in siphon skin makes an excitatory synapse with the motor neuron to the gill; with repeated stimulus, the excitatory responses (EPSPs) of the motor neuron decrease; this decrease is due to a decrease in the release of the neurotransmitter glutamate, by the sensory neuron
What is the Habituation Pathway for Aplysia?
Can last for 3-5 minutes (short-term memory), storage of this simple reflex memory is not restricted to a single synapse--change occurs across many synapses
How long does Habituation last?
Appears to be a common mechanism for habituation, less release of excitatory neurotransmitter
What is Synaptic Depression?
You get a smaller EPSP
What happens after Habituation?
An increase in the response to mild stimuli as a result of previous exposure to more intense stimuli; with aplysia, they become super sensitive to any kind of touch after being shocked repeatedly, storage of this simple reflex memory is not restricted to a single synapse,
What is Sensitization?
You get a larger EPSP (because serotonin causes increased glutamate responses)
What happens after Sensitization?
□ Tail stimulation (shock)→ sensory neuron→ faciliatory neuron→ facilitating interneuron→ regular interneuron→ gill motor neuron→ siphon motor neuron
What is the Sensitization Pathway in Aplysia?
Serotonin, serotonin causes an enhancement of synaptic transmission from the sensory neuron to the siphon to the motor neuron and an excitatory interneuron
What Neurotransmitter do the Faciliatory Interneurons use?
What is Synaptic Enhancement?
Synaptic enhancement occurs presynaptically; serotonin causes potassium channels to stay closed, allowing prolonged release of neurotransmitter (glutamate)
What is Serotonin's role in Sensitization?
About 40 sensory neurons in the abdominal ganglion innervate the siphon skin. These sensory cells terminate on a cluster of 6 motor neurons that innervate the gill and on several groups of excitatory and inhibitory interneurons that synapse on the motor neurons
What happens with the Gill Withdrawal Circuit?
Sensitization & Habituation
What are the two kinds of learning?
What are the connection between sensory neurons and motor neurons in Aplysia for Habituation?
What are the connection between sensory neurons and motor neurons in Aplysia for Sensitization?
Yes, repeated training by shocking the skin in aplysia can result in long-term changes in behavior
Can Aplysia develop long-term changes in behavior?
Increased glutamate by the sensory neuron
What are both types of Sensitization (Short-Term & Long-Term) due to?
Gradual, time is needed for protein synthesis
How fast is the change from short to long term sensitization?
By preventing the synthesis of: mRNA (encodes for proteins)-if you block this, you block long term memories (translation?) and proteins
How can long term memory formation be blocked without affecting short term memory?
An increase in synaptic structures, in addition to increase glutamate response
What does long term sensitization involve?
New protein synthesis is also needed for long-term habituation and this is because you need to break it down-need tools to do this
What does Long-Term Habituation require and why?
Pairing two stimuli together changes the response to one of them
What is Classical Conditioning (Associative Learning)?
Can the Withdrawal Reflex in Aplysia be Classically Conditioned?
Conditioning of the gill withdrawal reflex is achieved by pairing a strong stimulus (e.g. shock, the US) to one area (e.g. tail) preceded by a gentle stimulation (e.g. water jet, CS) to a different part (e.g. siphon), The CS must be paired immediately before or simultaneously with (but end before) the US
How can the Withdrawal Reflex be Classically Conditioned?
The US activates facilitating interneurons that synapse onto the axon terminals (axo-axonal synapse) of the conditioned sensory neuron, This arrangement causes synaptic facilitation, as in sensitization, Synaptic facilitation is enhanced by pairing of CS with US: CS produces action potentials in sensory neuron just prior to arrival of US, the resulting facilitation is therefore based on activity dependence; circuitry used here is the same as for sensitization
How does Classical Conditioning work with Sensitization?
Activity dependence is not only important for learning and memory but also for develop of pathways when the brain is growing
What is Activity Dependence?
Another common mechanism between development and learning
What are Sensitive Periods?
Guy who studied Aplysia & learning/memory (won Novel Prize)
Who is Eric Kandel?
Discovered by Hebb, also called Facilitated Synapses
What are Hebbian Synapses?
First described in the Hippocampus of rabbits, potentiation means an increase in the magnitude of response, LTP is a stable & enduring increase in the magnitude of the response of neurons after afferent neurons in the region have stimulated with bursts of electrical stimuli of moderately high frequency, LTP can be induced in the synapses of aplysia, it can be recorded from awake, freely moving animals that have learned
What is Long-Term Potentiation (LTP)?
Neurons from the medial temporal lobe cortex project to granule cells in the dentate gyrus. This path/those axons are called the perforant pathway (Think of the axons perforating the hippocampus to get to the dentate)--> The dentate granule cells send axons to pyramidal cells in the CA3 region of the hippocampus. This is the mossy fiber pathway--> The pyramidal cells of CA3 then project to the pyramidal cells in CA1. This is the Schaffer collateral fiber pathway--> the CA1 pyramidal cells then project out of the hippocampus
What is the Circuitry of the Hippocampus?
Specificity, Cooperativity, & Associativity
What are the 3 properties of LTP?
If some of the synapses onto a cell have been active during the strong stimulation and others have not, only the active ones become strengthened
What is Specificity?
Nearly simultaneous stimulation by two or more axons produces LTP, whereas stimulation by just one produces little to no response (this emphasizes paired activity)
What is Cooperativity?
Pairing a weak input with a strong input enhances a later response to the weak input; in this case, the weak input becomes potentiated (enhanced) only if it has been associated with the strong input
What is Associativity?
There are two types of glutamate receptor proteins (NMDA & AMPA) that both bind to glutamate; during stimulation by one input, glutamate binds to AMPA receptors (ionotropic receptors) to let sodium in; NMDA receptors are normally blocked by magnesium (Mg++), when strong inputs arrive (e.g., during associated or paired inputs), AMPA receptors let in a lot of sodium and the postsynaptic dendrite is depolarized a lot; this large depolarization causes the magnesium ions to leave the NMDA receptor, allowing glutamate to stimulate the NMDA receptor; the NMDA receptor now allows sodium and calcium into the postsynaptic neuron; calcium entry allow LTP to be induced
What is the Role of Glutamate Receptors?
Blocking calcium entry prevents LTP formation, calcium has to enter through NMDA receptor for LTP to form, entry of calcium causes changes in genes expression, as in long term sensitization in aplysia, this new gene expresion causes new synaptic structures to be built
What is the role of Calcium?
It doesn't appear to be the only physiological process that can occur during learning
Is LTP the basis of learning?