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Learning rules in cerebellar plasticity

Learning rules in cerebellar plasticity. Timing-based learning rules and coincidence detection: Behavioral - Cerebellar motor conditioning Molecular - IP 3 receptors Synaptic - Long-term depression at Purkinje neurons Spatial learning rules and spreading plasticity

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Learning rules in cerebellar plasticity

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  1. Learning rules in cerebellar plasticity • Timing-based learning rules and coincidence detection: Behavioral - Cerebellar motor conditioning Molecular - IP3 receptors Synaptic - Long-term depression at Purkinje neurons • Spatial learning rules and spreading plasticity • Tests and predictions

  2. In eyeblink conditioning, tone must precede airpuff by >80 msec.

  3. CALCIUM-DEPENDENT IP3 RECEPTOR DYNAMICS

  4. Cerebellar Purkinje neuron Denk, Sugimori and Llinás (1995) Proc. Natl. Acad. Sci. 92:8279-8282

  5. Denk, Sugimori, and Llinás (1995)

  6. Wang, Denk and Hausser (2000), Nature Neuroscience 3:1266

  7. Spine coincidence signals and LTD require calcium release

  8. What causes the timing-dependence of coincidence detection? • Time courses of glutamate, IP3, Ca2+ • Use-dependent facilitation • IP3R activation/inactivation by Ca2+ • IP3R activation/inactivation by IP3

  9. Conclusions (Part 1) • Two-photon measurements reveal a form of coincidence detection in single dendritic spines based on calcium release • The largest spine [Ca2+] elevations occur when presynaptic and postsynaptic activity are offset in time from each other • Offset timing rules may arise from IP3/Ca2+ dynamics or IP3 receptor dynamics • Parameters of cerebellar motor learning may correspond to the properties of IP3-dependent calcium release

  10. Chemical two-photon uncaging

  11. Wang, Khiroug and Augustine (2000) PNAS 97:8635

  12. LTD induction causes a spreading decrease in receptor sensitivity

  13. Furuta, Wang et al. (1999) PNAS 96:1193

  14. Comparison of a new caging group,6-bromo-7-hydroxycoumarin-4-ylmethyl (Bhc), with previous caged compounds

  15. SCANNING TWO-PHOTON UNCAGING OF GLUTAMATE

  16. Two-photon excitation: the third dimension of resolution

  17. Achieving a multiphoton effect by chemical means A new design principle: multiple-site caging Reduction of effective spontaneous hydrolysis Effective cross-section is MUCH larger (109-fold) than true two-photon excitation Chemical two-photon uncaging

  18. Wang and Augustine (1995)

  19. Double-caged IP3 Goal: uncaging IP3 in single dendritic spines. S.E. Gelber, D. Sarkisov, J.W. Walker, S.S.-H. Wang

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