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BIPN 148 Lecture 9. How are synaptic changes regulated? Malenka and Nicoll, 1995.

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Presentation on theme: "BIPN 148 Lecture 9. How are synaptic changes regulated? Malenka and Nicoll, 1995."— Presentation transcript:

1 BIPN 148 Lecture 9

2 How are synaptic changes regulated? Malenka and Nicoll, 1995

3 Biochemical Basis of LTP

4 Modulation of NMDA receptors

5 Calcium signaling and LTP/LTD

6 Calcium activation of CaM kinases

7 TTT CatalyticAutoinhibitorySelf-association Inhibitory Calmodulin Binding 286 Autonomous Activity 305/306 Inhibitory A BC PP Structure of CaMKII Verdaguer et al. (1999) Embo. J. 18:6329-6338.

8 Calcium activation of CaMKII

9 Persistent activation of CaMKII

10 NMDA Receptor CaMKII Transient CaMKII Activation Thr 286 Autophosphorylation (persistently active) NMDAR Association (persistently active) CaMKII Ca ++ / CaM Effects of Ca/CaM on CaMKII

11 CaM Kinase II and potentiation Wang and Kelly 1995

12 LTP in Thr286A mutant mice

13

14 Lissman, 1991 How might CaMKII affect synaptic function?

15 NR2B interaction with CaMKII

16 LTP-induced changes in AMPA currents

17 LTP phosphorylation of AMPA-R

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