Lecture 28: Molecular Mechanisms of Learning and Memory

What is associative learning?

change in behavioral response over time to repeated pairing of two different stimuli

What is conditioning?

repeated pairing of the CS and US (with CS slightly preceding US)

What is nonassociative learning?

change in behavioral response over time in response to a single type of stimulus

What are the two types of nonassociative learning?

habituation and sensitization

Define habituation.

decreased behavioral response over time to repeated stimulation

Define sensitization.

increased behavioral response over time to repeated stimulation 

What are the experimental advantages of invertebrate nervous systems?

• small nervous systems

• large neurons

• identifiable neurons

• identifiable circuits

What is important to know about habituation in Aplysia?

• mechanical stimulation of siphon with water jet results in gill withdrawal

• habituation results from synaptic modification between a sensory neuron and motor neuron

• repeated stimulation of the sensory neuron leads to progressively smaller EPSPs in motor neurons

• smaller EPSPs due to decrease in neurotransmitter release

• vesicle depletion: fewer vesicles released per AP over time

What is important to know about sensitization in Aplysia?

• brief electrical shock to the tail sensitizes the gill-withdrawal reflex

• involves the same sensory-motor circuit as habituation

• involves L29 (an interneuron) responds to tail-shock and synapses on the presynaptic terminal of the siphon sensory neuron

What is the sensitization mechanism pathway?

1. L29 releases serotonin in response to shock

2. serotonin receptors activate G-protein-coupled pathway

3. G-protein activation of adenylyl cyclase leads to increased cAMP

4. cAMP activates protein kinase A (PKA)

5. PKA phosphorylates K channels—causing them to close

6. presynaptic terminal is more depolarized—leading to increased Ca²⁺ entry when an AP arrives

7. increased Ca²⁺ entry leads to increased transmitter release

What are the two aspects of the Hebbian synaptic modification rule?

LTP and LTD

What is important to know about vertebrate synaptic plasticity?

• neurons that fire together, wire together

• neurons that are out of sync, lose think link

• mechanisms involving different types of glutamate receptors (AMPA, NMDA, and metabotropic)

Describe NMDA receptors.

• blocked by Mg²⁺ when postsynaptic cell is at resting potential

• conducts Ca²⁺ ions when postsynaptic cell is depolarized

• magnitude of Ca²⁺ influx through NMDA receptors can signal simultaneous firing of pre-synaptic and post-synaptic cells as needed for Hebbian learning

LTP in the hippocampus only affects syanpses that what?

are active when CA1 neurons are strongly depolarized

What does LTP in the hippocampus involve?

Ca²⁺ entry through NMDA channels

What does Ca²⁺ entry into CA1 neurons trigger?

• changes the effectiveness of existing AMPA receptors by phosphorylation

• stimulates insertion of new AMPA receptors into the postsynaptic membrane

True or False: LTP leads to presynpatic increase in neurotransmitter ability as well.

true

Generally, what is the BCM theory?

a theoretical model for bidirectional changes in synaptic strength (increases and decreases)

What are the BCM hypotheses?

• when the postsynaptic cell is weakly depolarized, active synapses undergo LTD

• when the postsynaptic cell is strongly depolarized, active synapses undergo LTP

Calcium-dependent mechanisms control the tradeoff between LTP and LTD. Describe these mechanisms.

• high frequency stimulation (HFS) → Ca²⁺ accumulation → protein kinase activation → LTP

• low frequency stimulation (LFS) → no Ca²⁺ accumulation → protein phosphatase activation → LTD

True or False: Segregation of retinal inputs to proper LGN layers occurs prior to visual experience. Inputs from the two eyes are not random; cells in each eye tend to fire in synchrony with their neighbors.

true

What is important to know about ocular dominance shifts in the striate cortex?

• visual experience results in correlated activity in corresponding RFs of left and right eyes

• normal: many neurons will have binocular receptive fields

• monocular deprivation: very few binocular neurons

Is there a critical period for plasticity of binocular connections?

yes, the most devastating effects occur when this plasticity is interrupted very early in life

What is the effect of strabismus on cortical binocularity?

• normal: percentage of neurons in layer III will form a bell-shaped curve

• strabismus: patients will experience two extremes in the ocular dominance groups