Cellular Mechanisms of Learning

Question 1

Model system Aplysia (sea slug) - why is it a motor system?

Answer 1

Exhibits a simple defensive withdrawal reflex which is influenced by learning and experience

Question 2

Gill and siphon withdrawal reflex

Answer 2

Tactile stimulus on the mantle shelf or the siphon causes reflexive withdrawal of the siphon and the gill

Question 3

Habituation and dishabituation experiment

Answer 3

Inserted photo cell under gill, stimulated the animal (photo cell was only triggered when the gill was contracted → made contact w/ light) → applied tactile stimulation to siphon → gill contracted a lot upon the first stimulation, did it less and less as it was repeated (dishabituation occurred after break in tactile stimulation)

Question 4

Associative learning (classical conditioning) experiment

Answer 4

Siphon stimulus (CS) paired with tail shock (US) → animal learned that siphon stimulus predicted tail shock → gill withdraws even without tail shock
Sensitization occurred when tail shock was delivered alone
Unpaired stimuli created no association → less siphon withdrawal

Question 5

Differential classical conditioning experiment

Answer 5

Two conditioned stimuli - tactile stimulus to siphon (CS1) and tactile stimulus to mantle (CS2)
Paired one with US (CS+) and the other wasn’t (CS-)
CS+ always resulted in increase in mean duration of siphon withdrawal (regardless of CS1 or CS2)
CS- had shorted duration (no association → no predictive power)

Question 6

Timing and order between CS and US

Answer 6

CS has to predict occurrence of US - specific time of CS coming one second before US (CS also always has to come first)

Question 7

Short term and long term effects in the context of sensitization

Answer 7

Trained for 4 days (1 trial/day) → retention lasted for about 12 days (only short term)

Question 8

Short term and long term effects in the context of habituation

Answer 8

Multiple trials on each day → able to show short term and long term effects (able to remember the stimulus is benign)
Total # of trials didn’t matter, pattern was more important (i.e. 40 trials spread out was more effective than all trials in one session)

Question 9

Neural mechanisms of learning - basics (specific to Aplysia)

Answer 9

Sensory neurons respond to tactile stimuli (responds more as force of stimulation increases - rate code) → motor neuron firing contracts gill (gill contracts more as force of stimulation increases - rate code)

Question 10

Neural basis of learning in Aplysia (neurons responsible for different body functions)

Answer 10

Head movements - buccal ganglion, cerebral ganglion
Sensory input & motor control of foot, tail, and body walls - pedal ganglion
Heart rate, blood circulation, and respiration - abdominal ganglion
Contains sensory neurons, interneurons, and motor neurons

Question 11

Neural architecture of gill withdrawal reflex

Answer 11

Pre-synaptic neurons (sensory neurons, facilitating interneuron) release neurotransmitters to post-synaptic neurons (motor neurons)
i.e. serotonin released from facilitating interneuron (cAMP-facilitated enhancement)

Question 12

Molecular basis of sensitization

Answer 12

Hormone/neurotransmitter (serotonin) ⇄ cAMP (release facilitated by adenyl cyclase) → activates protein kinase → allows PKA to phosphorylate (regulatory substrate is removed)

Question 13

Experiments to show neural mechanism of sensitization involves a presynaptic enhancement of synaptic strength - Experiment A

Answer 13

Stimulation of the tail input increased the EPSP from sensory to motor neuron

Question 14

Experiments to show neural mechanism of sensitization involves a presynaptic enhancement of synaptic strength - Experiment B

Answer 14

Stimulation of the sensory neuron + addition of serotonin → presynaptic mechanism enhancing synaptic strength

Question 15

Experiments to show neural mechanism of sensitization involves a presynaptic enhancement of synaptic strength - Experiment C

Answer 15

Stimulation of the sensory neuron + addition of cAMP → serotonin release from interneuron releases cAMP, enhancing synaptic strength

Question 16

Sensitization + classical conditioning in Aplysia both involve:

Answer 16

Repeated tail shocks and a facilitation of the response

Question 17

Experiment to show CS-US pairing (classical conditioning) role in US alone (sensitization)

Answer 17

One sensory neuron paired with tail shock, other sensory neuron not paired with anything → paired CS-US creates exaggerated motor neuron response, unpaired sensory neuron does not
Paired tactile CS activates sensory neurons just before the US, producing activity-dependent enhancement of synaptic transmission in the CS pathway

Question 18

Presynaptic facilitation contribution to CS-US

Answer 18

Serotonin produces a larger increase in cAMP in an active neuron than in an inactive neuron → Ca ions, due to activation of sensory neurons, “prime” the serotonin-dependent adenyl cyclase (sensitive to calcium ions)

Question 19

Cyclase coincidence detection in CS-US pairing

Answer 19

Output of cyclase is only amplified when neuronal activity is paired with a tail shock

Question 20

Comparisons of mechanisms of sensitization and classical conditioning

Answer 20

Classical conditioning produces more cAMP (more cyclase activity)
Ca^2+ is let in due to other sensory neuron being activated (no open channel in sensitization) → continues being active due to cyclase sensitivity to calcium
Calmodulin (protein) binding in classical conditioning also creates more cAMP

Question 21

Post-synaptic mechanisms during CS-US pairing

Answer 21

Sensitization → resting state, no current flows through the NMDA channel when post-synaptic membrane is not depolarized (channel is blocked by magnesium)
Classical conditioning → post-synaptic cell is depolarized, NMDA channel is activated, gives rise to Ca^2+ entry

Question 22

Experiment using APV to test role of NMDA receptors

Answer 22

Response of motor neuron decreased when APV was added (blocks NMDA receptors) only when CS-US pairing is established → NMDA receptors only play a role in classical conditioning
No response from motor neuron when hyperpolarized → have to incorporate post-synaptic mechanisms

Question 23

Neural mechanisms of sensitization in the context of long-term memory

Answer 23

Long-term sensitization can occur due to a permanent increase in motor neuron EPSP (occurs due to a permanent increase in neurotransmitter release from the presynaptic terminal)

Question 24

Experiment w/ sensitization and long-term memory

Answer 24

Condition with four trains of four shocks over four days displays long term memory (compared to fewer trains, fewer shocks, and fewer days)

Question 25

Changes that result in long-term memory of sensitization

Answer 25

New protein synthesis (translation) required for the structural changes in connections that accompany long-term processes