1. Plasticity in the nervous system Edward Mann 17 th Jan 2014

2. Lecture Plan How interactions with the environment change the brain Activity-dependent synaptic plasticity in the hippocampus Mechanisms of hippocampal synaptic plasticity Cellular learning rules – spike rate or spike timing?

3. Plasticity in neural circuits Ocular dominance columns

4. Plasticity in neural circuits Activity-dependent rewiring in visual cortex during development

5. Plasticity in neural circuits Environmental enrichment & spine density

6. Plasticity in neural circuits Associative learning through changes in synaptic weights

7. Lecture Plan How interactions with the environment change the brain Activity-dependent synaptic plasticity in the hippocampus Mechanisms of hippocampal synaptic plasticity Cellular learning rules – spike rate or spike timing?

8. Effects of bilateral temporal lobectomy - patient H.M. Scoville & Milner (1957) J Neurol Neurosurg Psychiat ‘In summary, this patient appears to have a complete loss of memory for events subsequent to bilateral medial temporal-lobe resection 19 months before, together with a partial retrograde amnesia for the three years leading up to his operation’

9. Long-term potentiation Bliss & Lomo (1973) J Physiol

10. Attractive features of LTP Input specificity

11. Attractive features of LTP Associativity (& Cooperativity)

12. Lecture Plan How interactions with the environment change the brain Activity-dependent synaptic plasticity in the hippocampus Mechanisms of hippocampal synaptic plasticity Cellular learning rules – spike rate or spike timing?

13. Mechanisms of LTP induction NMDA receptor-dependence

14. Mechanisms of LTP expression Increased AMPA receptor currents

15. Mechanisms of LTP maintenance Structural plasticity? Enger & Bonhoeffer (1999) Nature

16. Lecture Plan How interactions with the environment change the brain Activity-dependent synaptic plasticity in the hippocampus Mechanisms of hippocampal synaptic plasticity Cellular learning rules – spike rate or spike timing?

17. Hebb’s postulate When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased

18. Synaptic plasticity based on spike rates - the BCM model  synaptic strength Postsynaptic spike rate

19. Spike timing-dependent plasticity Bi & Poo (1998) J Neurosci

20. Spike rate and spike time encoding in the hippocampus Burgess & O’Keefe (2011) Current Opinion in Neurobiology

21. Compression of behavioural sequences for storage via STDP Dragoi (2013)

22. Replay of spike sequences during sleep From Daoyun Ji

23. Conclusion Neurons have the capacity to store information encoded by both spike rates and spike timing Understanding the biological basis of memory will require massively parallel recordings of both cellular and synaptic activity Advances in engineering and mathematical modelling are required to generate and interpret this data