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RCAN1 Regulates Bidirectional Synaptic Plasticity
Anthony Dudilot1, Emilie Trillaud-Doppia1, Jannic Boehm2
1Département Neurosciences, Groupe de Recherche sur le Système Nerveux Central, Université de Montréal, Montréal, QC H3T 1J4, Canada.
Abstract:
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.
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