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GluN3A excitatory glycine receptors control adult cortical and amygdalar circuits

2022; Cell Press; Volume: 110; Issue: 15 Linguagem: Inglês

10.1016/j.neuron.2022.05.016

1097-4199

Simon Bossi, Dhanasak Dhanasobhon, Graham C. R. Ellis‐Davies, Jimena Laura Frontera, Marcel de Brito Van Velze, Joana Lourenço, Alvaro Murillo, Rafael Luján, Mariano Casado, Isabel Pérez‐Otaño, Alberto Bacci, Daniela Popa, Pierre Paoletti, Nelson Rebola,

Receptor Mechanisms and Signaling

GluN3A is an atypical glycine-binding subunit of NMDA receptors (NMDARs) whose actions in the brain are mostly unknown. Here, we show that the expression of GluN3A subunits controls the excitability of mouse adult cortical and amygdalar circuits via an unusual signaling mechanism involving the formation of excitatory glycine GluN1/GluN3A receptors (eGlyRs) and their tonic activation by extracellular glycine. eGlyRs are mostly extrasynaptic and reside in specific neuronal populations, including the principal cells of the basolateral amygdala (BLA) and SST-positive interneurons (SST-INs) of the neocortex. In the BLA, tonic eGlyR currents are sensitive to fear-conditioning protocols, are subject to neuromodulation by the dopaminergic system, and control the stability of fear memories. In the neocortex, eGlyRs control the in vivo spiking of SST-INs and the behavior-dependent modulation of cortical activity. GluN3A-containing eGlyRs thus represent a novel and widespread signaling modality in the adult brain, with attributes that strikingly depart from those of conventional NMDARs.