1. Synaptic plasticity: Introduction Different induction protocols Calcium, NMDA receptors -And we will also have some formal stuff with how do we mathematically describe receptors, and talk some more about ODE’s

2. Rate based induction (show on board)

4. But: Heterosynaptic LTD – from Abraham (note – in vivo) Note about the different meanings of hetero Christie et. Al 1995

5. Pairing induced plasticity Feldman, 2000 Show voltage clamp

6. Spike timing dependent plasticity Markram et. al. 1997 Anatomy figure from Markram 97

7. Spike timing dependent plasticity Markram et. al. 1997

8. Bi and Poo J. Neurosci. 1998

9. Some properties (observations) of synaptic plasticity Synapse specificity (but) Associatively: LTP when pre and post occur together. Cooperativety: Two different input pathways can boost each other.

10. Some key elements of the biophysics of induction 1. NMDA receptors are necessary (in many systems) for the induction of LTP and LTD Bi and Poo, 1998 Control With APV Same holds for LTD – but some forms of plasticity are NMDAR independent

11. Partial blockade of NMDA-R Cummings et. al, 1996

12. There are two major types of excitatory glutamate receptors in the CNS: AMPA receptors And NMDA receptors II. Postsynaptic, channel openings.

13. Voltage dependent Calcium permeable Slow dynamics

14. Openings, look like: but actually

15. Openings, look like: How do we model this?

16. A simple option: Assume for simplicity that: Furthermore, that glutamate is briefly at a high value A max and then goes back to zero. SHOW ALSO MATRIX FORM

17. Assume for simplicity that: Examine two extreme cases: 1) Rising phase, α s (Glu max )>>β s :

18. Rising phase, time constant = 1/ α s (Glu max ) Where the time constant, τ rise = 1/(α s[Glu ]) τ rise

19. 2) Falling phase, [Glu]=0: rising phase combined

20. Simple algebraic form of synaptic conductance: Where B is a normalization constant, and τ 1 > τ 2 is the fall time. Or the even simpler ‘alpha’ function: which peaks at t = τ s

21. A more realistic model of an AMPA receptor Closed Open Bound 1 Bound 2 Desensitized 1 Markov model as in Lester and Jahr, (1992), Franks et. al. (2003). K 1 [Glu] K 2 [Glu] K -2 K -1 K3K3 K -3 K -d KdKd MATRIX FORM !!!

22. NMDA receptors are also voltage dependent: Jahr and Stevens; 90 Can this also be done with a dynamical equation? Why is the use this algebraic form justified?

23. The complete equation for current through the NMDAR should have several components: 1.Time dependence: 2.Multiply by voltage dependence of the conductance 3.And … how do you get a current for the conductance?

24. 2. Calcium influx is necessary for plasticity and its level determines the sign and magnitude of plasticity (Cho et. al. 2001)

25. And might be sufficient Yang, Tang Zucker, 1999

26. Moderate, but prolonged calcium elevation = LTD High calcium elevation = LTP ( brief is sufficient, but what will long do? ) Yang, Tang Zucker, 1999

27. High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD Magic High NMDA-R activation Modelrate NMDA-R activation

28. High/Correlated activity HighCalcium LTP Low/uncorrelated activity Moderate Calcium Calcium LTD LTD Magic High NMDA-R activation Modelrate NMDA-R activation

29. Oconnor et al. 2005

31. What did we learn today?