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Mechanisms of Long-Term Depression Induction in Purkinje Cells via Climbing Fiber Inputs

This study investigates the mechanisms of long-term depression (LTD) induction in Purkinje cells (PCs) through transient current injections and the role of AMPA receptors, mGluR1, and PKC activation. We analyze the pairing of parallel fiber-mediated EPSPs with depolarization and the effects of BAPTA and various inhibitors on LTD response. Additionally, findings from experiments involving L7-PKC transgenic mice highlight the involvement of PKC in VOR gain changes. Our research contributes to understanding the synaptic plasticity underlying cerebellar function and motor coordination.

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Mechanisms of Long-Term Depression Induction in Purkinje Cells via Climbing Fiber Inputs

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  1. 100 ms 10 mV 5 s

  2. 10 mV 5 s

  3. Transient current injection to the cell can toggle its state

  4. I V I V

  5. Climbing Fiber Parallel Fiber

  6. Climbing fibers response and Ca changes

  7. LTD: Long Term Depression

  8. LTD time course

  9. LTD: specificity PSTH: Post Stimulus Time Histogram

  10. LTD: Properties

  11. Involvement of AMPA receptors in LTD induction. Pairing PF-mediated EPSPs with depolarization of PCs Pairing quisqualate application with depolarization of cultured PCs

  12. BAPTA PKC (19¯36) Control PKC(glu27) (19¯36) Involvement of mGluR1 and PKC in LTD induction. control In the presence of antibodies inactivating mGluR1 The same in knockout mice lacking functional mGluR1

  13. Mechanism of LTD

  14. SS activity following vestibular stimulation CS activity following optical stimulation

  15. Mechanism of VOR gain change

  16. L7-PKC transgene

  17. Expression of PKC in L7-PKC mice

  18. LTD in L7-PKC mice Glutamate+Depolarization

  19. VOR gain change in L7-PKC mice

  20. Involvement of PKC activation in LTD induction. BAPTA PKC (19¯36) Control PKC(glu27) (19¯36) Control NOS inhibitor L-NMMA

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