Synaptic plasticity. Mark van Rossum. Institute for Adaptive and Neural Computation University of Edinburgh

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1 Synaptic plasticity Mark van Rossum Institute for Adaptive and Neural Computation University of Edinburgh 1

2 Human memory systems 2 Psychologists have split up memory in: Declarative memory * Episodic memory (personal what, when, where memories) - recollection - familiarity - hippocampus (patient HM) * Semantic memory: General facts about the world (cortex) Non-declarative memory (cortex, cerebellum,..) Motor skills, sensory processing,... Working memory (prefrontal, not discussed here)

3 Testing animal memory (Classical) conditioning Pavlov's dog Aplysia gill reflex Mazes and environments for rodents water maze place avoidance fear food location 3

4 Long term synaptic plasticity 4 What is (activity dependent, long term) synaptic plasticity? Long term, semi-permanent changes in the synaptic efficacy, induced by neural activity. In contrast to: - some aspects of development - short term changes - excitability changes

5 Memory systems Declarative memory * Episodic memory - recollection - familiarity - hippocampus (patient HM) * Semantic memory: General facts Non-declarative memory Motor skills, sensory processing,... 5 Synaptic plasticity

6 More reading Reviews of experimental LTP: - Kandel and Schwartz book - Hippocampus book Theory of Hopfield networks and Backpropagation - Herz, Krogh and Palmer Neural computation theory - Dayan & Abbott - Trappenberg 6

7 Bell Food Saliva For Aplysia see Kandel book NB: just a cartoon!

8 What fires together, wires together

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10 Diagram: Kit Longden

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14 Synaptic plasticity = memory? Criteria Detectability changes in behaviour and synaptic efficacy should be correlated Yes Mimicry change synaptic efficacies new apparent memory Rudimentary Anterograde alteration prevent synaptic plasticity anterograde amnesia Yes (e.g. NMDA block) Retrograde alteration alter synaptic efficacies retrograde amnesia Yes (e.g. PKMz), but... [Martin, Greenwood, Morris '04] 14

15 Synaptic plasticity=memory? [Whitlock,.. and Bear '06] 15

16 LTP stages Induction: - Requires pre- and post synaptic activity. - Mechanism: NMDA and Ca influx Expression - Early LTP - Late LTP Maintainance 16

17 NMDA requires pre and post activity, hence ideal for Hebbian Learning

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19 AP5 blocks learning [Morris et al 86] NMDA- block 19 NMDA- block

20 Ca hypothesis LTP [Bliss & Lomo '73] 20 LTD [O'Connor & Wang '05] Pairing high pre- and post synaptic activity => LTP Pairing with low activity => Long term depression

21 LTP stages Induction: - Requires pre- and postsynaptic activity. - Mechanism: NMDA and Ca influx Expression: - Early LTP (1 hr): - partly pre-synaptic changes - AMPAR phosphorylation - AMPAR insertion -Late LTP -? (requires protein synthesis) 21

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23 Changes in AMPA receptor phosphorilation 23 [Whitlock,.. and Bear '06]

24 Early phase LTP 24 CaMKII Stim.: 1 100Hz Rapid and local change

25 Associativity 25 Too weak LTP inducing Weak stim. no LTP Weak stim. paired with strong Associative LTP - Can be explained with voltage dependence of NMDA - Associative learning such as Classical conditioning (Pavlov)

26 Bell Food Saliva For Aplysia see Kandel book NB: just a cartoon!

27 Early phase LTP Stim.: 1 100Hz Rapid and local change 27 But gone after few hours

28 Late LTP requires protein synthesis 28 [Fonseca et al 06]

29 Late phase LTP 29 Stim: 3x ) PRPs Dopa mine Start protein synthesis Ship PRPs to tagged synapses LTP lasts

30 LTP stages Induction: - Requires pre- and post synaptic activity. - Mechanism: NMDA and Ca influx Expression: - Early LTP (1 hr): - partly pre-synaptic changes - AMPAR phosphorylation - AMPAR insertion -Late phase LTP -requires protein synthesis 30

31 What determines if LTP lasts? 31 Reward and punishment [Seidenbecher '95]

32 Longevity: In vivo physiology 32 [Abraham '02] Strong extracellular stimulation, leads to long lasting strengthening of synapse [Bliss and Lomo '73]

33 What determines if LTP lasts? 33 Stimulus protocol [Abraham '00] Environment [Abraham '02, Li & Rowan '00] (Dopamine mediated) Does a novel environment 'reset' hippocampal learning?

34 LTP stages Induction Expression Maintainance 34

35 LTP maintenance as an active process ZIP disrupts one month old memory [movie demo] 35 [Pastalkova et al '06]

36 Hypotheses for maintaince / long term stability Slots for AMPA receptors [Turrigiano '02] GluR2 trafficking [Yao & Sacktor '08] 36

37 Spine plasticity Yu Zuo Curr Opin Neurobiol (2010) 37

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