Current Biology
Volume 30, Issue 7, 6 April 2020, Pages 1167-1176.e2
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Article
RCAN1 Regulates Bidirectional Synaptic Plasticity

https://doi.org/10.1016/j.cub.2020.01.041Get rights and content
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Highlights

  • Inhibiting GSK3β-dependent phosphorylation of RCAN1 increases synaptic transmission

  • Inhibiting GSK3β-dependent phosphorylation of RCAN1 blocks LTD induction

  • Inhibiting phosphorylation of RCAN1 at a PKA site blocks LTP induction

  • RCAN1 regulates bidirectional synaptic plasticity through its regulation of calcineurin

Summary

Synaptic plasticity, with its two most studied forms, long-term potentiation (LTP) and long-term depression (LTD), is the cellular mechanism underlying learning and memory. Although it has been known for two decades that bidirectional synaptic plasticity necessitates a corresponding bidirectional regulation of calcineurin activity, the underlying molecular mechanism remains elusive. Using organotypic hippocampal slice cultures, we show here that phosphorylation of the endogenous regulator-of-calcineurin (RCAN1) by GSK3β underlies calcineurin activation and is a necessary event for LTD induction, while phosphorylation of RCAN1 at a PKA site blocks calcineurin activity, thereby allowing LTP induction. Our results provide a new mechanism for the regulation of calcineurin in bidirectional synaptic plasticity and establish RCAN1 as a “switch” for bidirectional synaptic plasticity.

Keywords

synaptic plasticity
synaptic transmission
RCAN1
calcineurin
PKA
GSK3beta
long-term depression
long-term potentiation

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