Involvement of a calcineurin/ inhibitor-1 phosphatase cascade in hippocampal long-term depression (original) (raw)

Nature volume 369, pages 486–488 (1994)Cite this article

Abstract

LONG-TERM potentiation (LTP) is a synaptic mechanism thought to be involved in learning and memory1. Long-term depression (LTD), an activity-dependent decrease in synaptic efficacy, may be an equally important mechanism which permits neural networks to store information more effectively2,3. One form of LTD that has been observed in the hippocampus4 requires activation of post-synaptic NMDA (_N_-methyl-d-aspartate) receptors4,5, a change in postsynaptic calcium concentration5, and activation of postsynaptic serine/threonine protein phosphatase 1 (PP1) or 2A (PP2A) 6. The mechanism by which PP1 or PP2A is regulated by synaptic activity is unclear because these protein phosphatases are not directly influenced by calcium concentration. LTD induction may require activation of a more complex protein phosphatase cascade consisting of the Ca2+ /calmodulin-dependent protein phosphatase, calcineurin, its phosphoprotein substrate, inhibitor-1, and PP17,8. We tested this hypothesis using calcineurin inhibitors as well as different forms of inhibitor-1 loaded into postsynaptic cells. Our results suggest a signalling pathway in which calcineurin dephosphorylates and inactivates inhibitor-1. This in turn increases PP1 activity and contributes to the generation of LTD.

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Author notes

  1. Robert C. Malenka: To whom correspondence should be addressed

Authors and Affiliations

  1. Departments of Psychiatry & Physiology, University of California, San Francisco, California, 94143-0984, USA
    Rosel M. Mulkey & Robert C. Malenka
  2. Department of Pharmacology, Duke University Medical Center, Durham, North Carolina, 27710, USA
    Shogo Endo & Shirish Shenolikar

Authors

  1. Rosel M. Mulkey
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  2. Shogo Endo
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  3. Shirish Shenolikar
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  4. Robert C. Malenka
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Mulkey, R., Endo, S., Shenolikar, S. et al. Involvement of a calcineurin/ inhibitor-1 phosphatase cascade in hippocampal long-term depression.Nature 369, 486–488 (1994). https://doi.org/10.1038/369486a0

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