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Updated: Jul 28, 2025

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Published on: February 4, 2014
Excitatory GluN1/GluN3A glycine receptors (eGlyRs) in brain signaling
Simon Bossi1, Lara Pizzamiglio1, Pierre Paoletti1
1Institut de Biologie de l'École Normale Supérieure (IBENS), Ecole Normale Supérieure, Université PSL, CNRS, INSERM, F-75005 Paris, France.
Abstract:
GluN3A is a glycine-binding subunit belonging to the NMDA receptor (NMDAR) family that can assemble with GluN1 subunits to form unconventional NMDARs insensitive to glutamate and activated by glycine only. The existence of such excitatory glycine receptors (eGlyRs) in the central nervous system (CNS) has long remained elusive. Recently, eGlyRs have been identified in specific brain regions, where they represent a novel neuronal signaling modality by which extracellular glycine tunes neuronal excitability, circuit function, and behavior. In this review, we summarize the emerging knowledge regarding these underappreciated receptors. The existence of eGlyRs reshapes current understanding of NMDAR diversity and of glycinergic signaling, previously thought to be primarily inhibitory. Given that GluN3A expression is concentrated in brain regions regulating emotional responses, eGlyRs are potential new targets of therapeutic interest in neuropsychiatry.
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