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Related Experiment Videos

Reversing cerebellar long-term depression.

Varda Lev-Ram1, Samar B Mehta, David Kleinfeld

  • 1Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093-0647, USA.

Proceedings of the National Academy of Sciences of the United States of America
|December 13, 2003
PubMed
Summary
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Postsynaptic long-term potentiation (LTP) in cerebellar Purkinje cells, mediated by nitric oxide (NO), can reverse and reset long-term depression (LTD). This NO-dependent postsynaptic LTP acts as a true counterbalance to LTD.

Area of Science:

  • Neuroscience
  • Cellular Neuroscience
  • Synaptic Plasticity

Background:

  • Cerebellar long-term depression (LTD) is a key form of synaptic plasticity.
  • The existence of a postsynaptic form of cerebellar parallel fiber-Purkinje cell long-term potentiation (LTP) suggests a potential resetting mechanism for LTD.

Purpose of the Study:

  • To investigate whether postsynaptic LTP can reverse saturated LTD.
  • To determine the mechanisms underlying postsynaptic LTP and its relationship with LTD.

Main Methods:

  • Extracellular monitoring of Purkinje cell (PC) spikes for stable synaptic efficacy recordings.
  • Induction protocols for both LTD and postsynaptic LTP.
  • Application of nitric oxide (NO) and forskolin.
  • Investigating the roles of postsynaptic Ca2+ elevation and cAMP.

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Main Results:

  • Saturated LTD can be reversed by postsynaptic LTP or nitric oxide (NO), allowing reinduction of LTD.
  • Saturated postsynaptic LTP can be reversed by LTD.
  • Presynaptic LTP or forskolin application does not reverse saturated LTD.
  • Postsynaptic LTP mediated by NO without postsynaptic Ca2+ elevation effectively counterbalances LTD.

Conclusions:

  • Postsynaptic LTP, particularly when mediated by NO without postsynaptic Ca2+ elevation, serves as a true counterbalance to LTD.
  • This contrasts with presynaptic LTP, which is mediated by cAMP and does not reverse saturated LTD.