Memory Mechanisms in Aplysia- 2

Question 1

Conditioning in Aplysia- circuitry

Answer 1

DIAGRAM

Question 2

Components affected after induction (forward pairing)

Answer 2

DIAGRAM

Question 3

During forward pairing…

Answer 3

…CS opens Ca2+ channels –> activates calmodulin –> primes adenylyl cyclase –> increased catalytic activity increase cAMP –> increased PKA activity –> increase NT release

Question 4

Pairing of the CS pathway activation with the presynaptic facilitation induced by the US leads to increased NT release during induction:

Answer 4

–> activation of Glu-Rs during induction

larger MN EPSPs and associated postsynaptic depolarisation during induction

Question 5

How is conditioning different from sensitisation in Aplysoia?

Answer 5

Increased NT release only seen once the tactile stimulation of the siphon is resumed (there is no activation of the SN from the siphon during induction (sensitisation)

Question 6

Blocking NMDA-Rs during conditioning paradigm…

Answer 6

…prevents the enhancement of MN EPSPs

Question 7

Presynaptic coincidence detector in conditioning in Aplysia

Answer 7

Adenylyl cyclase: CS (↑[Ca2+]) + US (5HT receptors) leads to ­ AC turnover rate than either CS or US alone
↑ L-glu release to each CS
Detect CS/US forward pairing directly (presynaptic locus)

Question 8

Postsynaptic coincidence detector in conditioning in Aplysia:

Answer 8

Requires facilitated presynaptic response to CS + US to release L-glu and US to depolarize MN via excitatory interneurones
Detect CS+/US pairing indirectly through the larger EPSP generated by the ↑ in L-glu release (postsynaptic locus)
Reinforces 1st via retrograde signalling by a +ve feedback pathway to AC

Question 9

Function of coincidence detectors in Aplysia

Answer 9

Detect the coincidence of the CS with US and modify synaptic function, both mechanisms are associative

Question 10

Compare LTP in Aplysia with Hebbian LTP in mammalian systems

Answer 10

come back to this !!!

Question 11

Summary of short term learning in Aplysia

Answer 11

TABLE

Question 12

Why are mechanisms like biochemical up or down regulation not suitable for long term memory?

Answer 12

Prolonged biochemical up or down regulation is inefficient. It could become saturated so that learning would cease - memory full.

Question 13

Determinants of extent of long term memory

Answer 13

Massed learning VS repeated learning

Question 14

Distributed learning for habituation in Aplysia

Answer 14

Tactile stimulation - 40 trials in total
10 trials given on each of 4 training days (T1, T2, T3 and T4).
Retention tested after 1, and then either 7 and 21 days (R1, R2 and R3).
Habituation still present after 21 days.

Question 15

Massed learning for habituation

Answer 15

40 trials given in 1 training session (day 4 only - equivalent T4 see
arrow) –> massed learning produces far less retention or LTM than distributed learning

Question 16

LTM for sensitisation in Aplysia

Answer 16

Test response: siphon or gill withdrawal
to non-noxious tactile stimulus
Inducing stimuli: electric shock 1s duration Single shocks 30-120min apart
Trains - 3s interval (0,3,6,9s), 30min apart
4 trains of 4 tails shocks over 4 days, 1 train of 4 tails shocks per day - distributed
4 trains of 4 tail shocks in a single day - massed
4 single tail shocks (not a train) on a single day.
Again repetition (distributed learning) → better memory retention

Question 17

Pharmacological imitation of LTM in Aplysia?

Answer 17

Sensitization mimicked by application of 5HT directly on to the sensory neurone-motor neurone (SN-MN) synapse.
One application induces synaptic facilitation that lasts 15 min. (short-term).
Five applications evenly spaced over 90 min. (1 every 22.5 min.) induces synaptic facilitation that lasts over 24 hours (long-term)

Question 18

Protein synthesis and LTM in Aplysia?

Answer 18

Transcription blocker (actinomycin D) and translation blocker (anisomycin) both block LTM only if delivered during training trials, have no effect on STM

Question 19

Function of newly synthesised proteins in sensitisation?

Answer 19

Sensory neurones show greater axonal branching following long term sensitisation, form new neurites and synapses (synaptogenesis)

Question 20

Changes in sensory neurone varicosities following LTM?

Answer 20

Number of varicosities doubles after long term sensitisation

Number decreases following long term habituation

Question 21

What triggers the formation of new synaptic proteins?

Answer 21

5-HT –> ↑ cAMP –> ↑ PKA –> phosphorylation of CREBs by PKA –> transcription of IEGs (usually TFs)

Question 22

IEGs activate….

Answer 22

LRGs

IEG transcription –> TFs (directed to nucleus to facilitate LRG transcription) –> LRG transcription –> Proteins (synaptic components)

Question 23

Compare the activation period of IEGs and LRGs

Answer 23

IEG «< LRG

Question 24

Where are LRGs directed to?

Answer 24

Axon terminal/ plasma membrane (can be ion channels, receptors, IC signalling proteins, cytoskeletal proteins, synaptic vesicle proteins)

Question 25

Initiation of de novo protein synthesis

Answer 25

1. PKA phosphorylates CREB proteins
2. CREB-1 binds with CRE
3. IEG transcription activated (mRNA)
4. IEG-translated protein
   activates LRG
5. LRGs transcription activated and mRNAs translated to proteins

Question 26

What do inhibition of CREB-1 cause?

Answer 26

Prevention of long term sensitisation

Question 27

What does injecting phosphorylated CREB-1 cause?

Answer 27

Induction of facilitation of motor neurone EPSP