Excitatory GluN1/GluN3A glycine receptors (eGlyRs) in brain signaling

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 extra cellular 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.

Automated summary

GluN3A is a subunit of the NMDA receptor family that can form glycine-activated receptors with GluN1 subunits. These excitatory glycine receptors (eGlyRs) have been discovered in specific brain regions and play a role in regulating neuronal excitability and behavior. The existence of eGlyRs expands our understanding of NMDAR diversity and glycinergic signaling, which was previously thought to be inhibitory. Given their concentration in brain regions regulating emotional responses, eGlyRs are potential therapeutic targets in neuropsychiatry.