Synaptic plasticity: Introduction

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) Christie et. Al 1995 Note about the different meanings of hetero

5. Pairing induced plasticity Feldman, 2000 Show voltage clamp

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

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 Control With APV Bi and Poo, 1998 Same holds for LTD – but some forms of plasticity are NMDAR independent

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

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

13. Voltage dependent • Calcium permeable • Slow dynamics

14. Openings, look like: but actually

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

16. How do we model this? A simple option: Assume for simplicity that: SHOW ALSO MATRIX FORM Furthermore, that glutamate is briefly at a high value Amax and then goes back to zero.

17. Assume for simplicity that: Examine two extreme cases: 1) Rising phase, αs(Glumax )>>βs:

18. Rising phase, time constant = 1/ αs(Glumax ) Where the time constant, τrise= 1/(αs[Glu]) τrise

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

20. Simple algebraic form of synaptic conductance: Where B is a normalization constant, and τ1 > τ2is the fall time. Or the even simpler ‘alpha’ function: which peaks at t= τs

21. Bound 1 Closed Open Bound 2 K1[Glu] K2[Glu] K3 K-1 K-2 K-3 Kd K-d Desensitized 1 Markov model as in Lester and Jahr, (1992), Franks et. al. (2003). A more realistic model of an AMPA receptor 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: • Time dependence: • Multiply by voltage dependence of the conductance • 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. Magic Magic LTP LTD High/Correlated activity Low/uncorrelated activity High NMDA-R activation Modelrate NMDA-R activation High Calcium Moderate Calcium LTP LTD

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

29. Oconnor et al. 2005

31. What did we learn today?