lecture 9 - neural mechanisms of learning and memory

Question 1

what type of neural wiring supports memory?

Answer 1

diagram in notes

plasticity in a superordinate circuit
- third connection or neuron that modifies communication - enhances it or stops it

Question 2

neural process before training

Answer 2

changes involving synaptic transmitters

diagram in notes

Question 3

habituation

Answer 3

Habituation, is a simple form of learning - only one stimulus is
learned about.
◦ The automatic response to a stimulus is REDUCED over repeated
presentation of that stimulus.

Question 4

Habituation in Aplysia:
Gill withdrawal response

Answer 4

innate/ automatic response to protect breathing apparatus

so any part of the slug you touch around the Gil will lead it to withdraw in order to protect it

the duration of a gill withdrawal tells us how much its learnt about that given stimulation

what you expect to see with habituation is if you keep prodding the siphon area it will initially have a really big response, after a few touches it will realise its non threatening and reduce the duration of the gill withdrawal

Question 5

why study aplysia?

Answer 5

diagram in notes

you look at the individual neurone and measure what’s happening at the synaptic level while your measuring what’s going on in the gill

at the behavioural level
after touching the siphon, the motor neurone leads to the gill withdrawal response

you use a tactile stimulation eg a paintbrush to prod the siphon to make the slug withdraw the gill. initially there is a big response and after repeated trails it will reduce - an example of habituation

Question 6

habituation in the aplysia - neuronal level

Answer 6

connection between a sensory neurone and a motor neurone

the siphon being touched then gets the sensory neurone to fire then the motor neurone and leads to a gill withdrawal response

the motor neurone is the part that makes a part of your body move

during habituation even though the sensory neurone fires but the motor neurone reduces firing as withdrawal is no longer needed - this reaction is not due to cell death - its not that the motor neurone has stopped working its just not responding to the sensory neurone anymore

habituation shows short-term and long-term memory - can relate hm mirror drawing task learning to habituation as over time learning is retained between sessions - there is a bit of forgetting in-between

Question 7

short-term habituation - reduction in neurotransmitters

Answer 7

in ST habituations there is a decrease in the amount of glutamate that is released by the sensory neurone. this is measured by quantal analysis. - it measures how much neurotransmitter has been released into a synapse. this means the motor neurone is weakly stimulated so it will stop responding

Question 8

long- term habituation - change in synapse structure

Answer 8

the number of connections between the sensory neurone and motor neurone are reduced to one rather than 3. this is the same in humans, monkeys and rats.

evidence that changes in synaptic connections and how readily those synapses stimulate the next neurone and leads to learning

a weakening in connection leads to less responding

after a day of habituation 90 connections, after a week 80

Question 9

learning

Answer 9

a decrease in behaviour is less connections between neurones or fewer connections between neurones

learning is a result of strengthening and weakening connections between synapses

Question 10

Habituation:
Interim summary

Answer 10

Not caused by sensory fatigue or by damage to the motor neuron
* Short-term habituation is due to a decrease in the amount of neurotransmitter released by the sensory neuron.
* Long-term habituation mediated by changes in the physical structure of the network.
Process is termed HOMOSYNAPTIC DEPRESSION

pathway specific - only for one stimulus

Question 11

sensitisation

Answer 11

• Your behavioural response is increased / amplified
• Essentially the opposite of habituation
  Usually due to heightened arousal - body is in an alert state
  increase in response

Question 12

sesnsitiastion is aplysia

Answer 12

apply a extremely weak stimulus to the siphon you see a modest withdrawal of the gill

then we frighten the animal and give a big stimulus to the tail and it causes a contraction that lasts for a few seconds so after a minute and you touch the siphon it has a much bigger response

sensitisation is a increased withdrawal response to stimulation because your in an alert state even if the touch to the siphon is gentle

if you give them a few tail shocks the duration of gill withdrawal is a really long time initially and overtraining that reduces

for single shocks an increase in responding and then that will reduce again overtime due to forgetting so after training you get a long term memory so it maintains that high alert status

sensitisation happens anywhere in the animal so its a system wide change as whole animal is in state of shock unlike habituation which is very specific

Question 13

what happens at the cellular level?

Answer 13

sensory neurone is firing and motor neurone is firing a little bit then you sensitise the animal so its more scared and apply the stimulus to the sensory neurone so it fires and you see a bigger response in the motor neurone

an interneuron also influences how much the sensory neurone fires so can increase what the motor neurone response might be

Question 14

normal sensorimotor processing

Answer 14

looks like a superordinate circuit!
So, normal synaptic transmission looks like
this: sensory —-> motor
Then add in a tail shock…
the superordinate circuit comes in and modifies the connection
the interneuron synapses with the sensory neurone and influences how it talks to the motor neurone
after the tail shock the interneuron releases serotonin (5HT) to facilitate the release of more glutamate from the sensory neurone when its stimulated when you touch the siphon so means motor neurone is more likely to fire leading to the big withdrawal response

Question 15

Spike broadening

Answer 15

learning as a result of changes in how the neurones are connecting with each other
* Increase in neurotransmitter released as a result of a few processes
* Closing K+ channels-> when sensory neuron activated more Ca2+ -> more transmitter release into the synapse
* Remember this is a SYSTEM-WIDE change – so all sensory neurons will have this engaged
* Contrast with habituation – DECREASE in neurotransmitter release
These processes support short-term changes in neurotransmitter release
What about Long-term changes? Growth of new synapses between sensory and motor neurons

Question 16

Conclusion

Answer 16

• Eric Kandel showed (for the first time) that learning was caused by changes in synaptic strength. Before it was just theory.
• Aplysia displays habituation through changes in the pre-synaptic release of the neurotransmitter glutamate.
• Habituation linked to decrease in neurotransmitter release from sensory neuron.
• Sensitization linked to an increases in neurotransmitter release from the sensory neuron.

Studying simple forms of learning in Aplysia confirm synaptic plasticity underpins learning and that both increases and decreases in the strength of connection between neurons can support learning and memory.

Question 17

“The Cellular Mechanisms of Learning in Aplysia: Of Blind Men and Elephants” by David L. Glanzman,:

Answer 17

🧠 Overview
Challenges the traditional view that learning in Aplysia is driven solely by presynaptic mechanisms.
Argues that postsynaptic changes are critical for both nonassociative (habituation, sensitization) and associative learning.
Draws parallels between Aplysia and mammalian learning, especially regarding AMPA receptor trafficking and NMDA receptor involvement.
🧪 Key Findings
1. Habituation

Long-term habituation (LTH) depends on:
Protein synthesis & gene expression
Postsynaptic NMDA & AMPA receptor activation
Protein phosphatases (PP1, PP2A) & calcineurin
Evidence from C. elegans shows LTH also involves postsynaptic AMPA receptor downregulation, not presynaptic mechanisms.
2. Sensitization

Previously thought to be purely presynaptic (serotonin-triggered facilitation).
Now shown to involve:
Postsynaptic Ca²⁺ release from intracellular stores
Exocytosis leading to AMPA receptor insertion
Greater enhancement of AMPA- vs. NMDA-mediated EPSPs
Disruption of dishabituation when postsynaptic mechanisms are blocked
🔁 Associative Learning
Classical conditioning of the gill-withdrawal reflex requires:
Hebbian, NMDA-dependent LTP
Postsynaptic Ca²⁺ influx and signaling
Suggests coordinated pre- and postsynaptic plasticity via retrograde signaling.
🔬 Mechanistic Model
Short-term learning may involve only presynaptic changes.
Long-term learning requires:
Retrograde signals from motor neurons
Postsynaptic Ca²⁺-dependent activation of signaling pathways
AMPA receptor trafficking
🧬 Broader Implications
AMPA receptor trafficking is a conserved mechanism shared across species, including mammals.
Draws parallels to LTP in mammalian hippocampus.
Argues that underestimating postsynaptic contributions in invertebrates has limited their perceived relevance to neuroscience.
📌 Conclusion
Aplysia learning involves both pre- and postsynaptic changes, especially for persistent memory.
Postsynaptic mechanisms are essential, not just accessory.
Encourages revisiting and rebalancing models of synaptic plasticity across species.
Suggests future work should explore interneuronal contributions and trans-synaptic coordination.