Role of NMDA receptor subtypes in regulation of central amygdala

Abstract

We have recently shown that mice lacking the NMDA receptor GluN2C (GluN2C KO) subunit exhibit deficits in contextual and cued fear acquisition (Hillman et al., 2011). The central amygdala (CeA) is composed of lateral (CEl) and medial (CEm) subnuclei which are involved in fear acquisition and expression respectively. Furthermore, CEloff neurons are characterized as PKCδ‐positive, tonically inhibit the CEm resulting in regulation of fear expression. We found that in comparison to wildtype, GluN2C het and KO mice have over two‐fold pERK stained neurons in the CEl which co‐localizes with PKCδ. Additionally increased frequency of sIPSCs was observed in CEm of GluN2C KO versus wildtype mice. We sought to determine if potentiation of GluN2Ccontaining receptors would alleviate fear acquisition deficit in GluN2C heterozygous mice. D‐cycloserine, which has two‐fold efficacy at GluN2C‐containing receptors compared to glycine, injected prior to fear conditioning increased fear acquisition in GluN2C heterozygous animals while it had no effect on knockout counterparts. A potential role of GluN2C receptors expressed in mediodorsal thalamus was further identified in regulating CEl activity. The findings presented herein show that GluN2C subunit may regulate basal CeA activity which may have important implication for anxiety and fear disorders.