1. DENT/OBHS 131Neuroscience synaptic plasticity 2009

2. Learning objectives • Understand the properties of long-term potentiation (LTP) that define it as a model of experience-dependent synaptic plasticity • Discuss the characteristics that make NMDA receptors coincident detectors cable of initiating associative information storage (Pavlov’s dog) • Describe the relationship between NMDA receptors, LTP and behavioral memory

3. learning & memory in taxi drivers • PET study during recall of London route (Maguire et al, 1997)

4. Papez circuit / loop

5. place cells / maps • some pyramidal cells in the hippocampus (and other parts of Papez circuit) have preferred spatial orientations & place maps (O’Keefe & Dostrovsky, 1971)

6. Hebbian learning….in theory • longer term plasticity • Hebbian learning • Hebb (1949) hypothesized that “ if one neuron frequently takes part in exciting another, some growth process or metabolic change takes place in one or both cells and the strength of their connection increases ”

7. Synapses are plastic • synapses “remember” previous activity • short-term, e.g. post-tetanic potentiation at the nmj control motor neuron motor neuron pre nmj muscle muscle time post

8. Can synaptic plasticity explain learning? • CS (neutral) - no response • US - UR • After pairing: • CS - CR

9. Learning Objective #1 • Understand the properties of long-term potentiation (LTP) that define it as a model of experience-dependent synaptic plasticity

11. Long-term potentiation (LTP) • first demonstration of LTP • high-frequency train • rapid induction • lasts weeks in vivo after before amplitude time (hrs) Bliss & Lomo (1973)

12. properties of LTP

13. Learning Objective #2 • Discuss the characteristics that make NMDA receptors coincident detectors cable of initiating associative information storage (Pavlov’s dog)

14. cellular mechanisms underlying LTP • induction • maintenance

15. excitatory synaptic transmission • NMDA vs non-NMDA • synaptic transmission AP5 control AP5

16. LTP depends specifically on NMDA receptor activation • AP5 prevents high frequency-induced LTP (Collingridge et al, 1983)

17. out +++ Mg+ Mg+ - - - in what is special about NMDA receptors? • voltage-gated channels: voltage • ligand-gated channels: transmitter • NMDA receptors: both + - +

18. NMDA receptor: a molecular switch • co-incidence detector • requires both presynaptic activity (glutamate) and postsynaptic depolarization (relieve Mg block) • satisfies Hebbian co-incidence rules • explains LTP properties:

19. how does the NMDA receptorcause a change in synaptic strength?

20. synaptic transmission is unreliable • increased transmitter release • altered or new receptors • new synapses

21. hippocampal “integrated circuit” Johnson & Wu (1995)

22. associative pattern storage from McNaughton & Morris (1987)

23. Learning Objective #3 • Describe the relationship between NMDA receptors, LTP and behavioral memory

24. NMDA receptor-dependent learning spatial memory task visual task “Morris” water maze Morris et al (1990)

25. LTP and learning • saturation of LTP prevents learning a new spatial task • new learning can occur after LTP decay LTP decay Castro et al (1989)

26. diffuse storage in cortex? • computational theories • e.g., Marr (1970’s) • sensory input to neocortex • stored by association • repetition - association • partial pattern recall