Metaplasticity Gated Through Differential Regulation of GluN2A Versus GluN2B Receptors by Src Family Kinases

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2011 Dec 22

PMID 22187052

Citations 46

Authors

Kai Yang

Catherine Trepanier

Bikram Sidhu

Yu-Feng Xie

Hongbin Li

Gang Lei

Michael W Salter

Beverley A Orser

Takanobu Nakazawa

Tadashi Yamamoto

Michael F Jackson

John F Macdonald

Affiliations

Soon will be listed here.

Abstract

Metaplasticity is a higher form of synaptic plasticity that is essential for learning and memory, but its molecular mechanisms remain poorly understood. Here, we report that metaplasticity of transmission at CA1 synapses in the hippocampus is mediated by Src family kinase regulation of NMDA receptors (NMDARs). We found that stimulation of G-protein-coupled receptors (GPCRs) regulated the absolute contribution of GluN2A-versus GluN2B-containing NMDARs in CA1 neurons: pituitary adenylate cyclase activating peptide 1 receptors (PAC1Rs) selectively recruited Src kinase, phosphorylated GluN2ARs, and enhanced their functional contribution; dopamine 1 receptors (D1Rs) selectively stimulated Fyn kinase, phosphorylated GluN2BRs, and enhanced these currents. Surprisingly, PAC1R lowered the threshold for long-term potentiation while long-term depression was enhanced by D1R. We conclude that metaplasticity is gated by the activity of GPCRs, which selectively target subtypes of NMDARs via Src kinases.

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