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Science. 2019 Oct 11;366(6462):250-254. doi: 10.1126/science.aax1522.

Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula.

Author information

1
Institut de Biologie de l'École Normale Supérieure (IBENS), INSERM U1024, CNRS UMR8197, École Normale Supérieure, Université PSL, 75005 Paris, France.
2
Department of Psychiatry, School of Medicine, Douglas Hospital Research Center, McGill University, Montreal, QC H4H 1R3, Canada.
3
Sorbonne Université, CNRS, INSERM, Neurosciences Paris Seine - Institut de Biologie Paris Seine (NPS-IBPS), 75005 Paris, France.
4
Laboratory of Thalamus Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary.
5
Research Centre for Natural Sciences Institute of Cognitive Neuroscience and Psychology, 1117 Budapest, Hungary.
6
Department of Anatomy and Histology, University of Veterinary Medicine, 1078 Budapest, Hungary.
7
Integrative Neuroscience and Cognition Center, CNRS UMR8002, Glia-Glia and Glia-Neuron Interactions Group, Paris Descartes University, 75006 Paris, France.
8
Sorbonne Université, CNRS, INSERM, Neurosciences Paris Seine - Institut de Biologie Paris Seine (NPS-IBPS), 75005 Paris, France. marco.diana@upmc.fr.

Abstract

The unconventional N-methyl-d-aspartate (NMDA) receptor subunits GluN3A and GluN3B can, when associated with the other glycine-binding subunit GluN1, generate excitatory conductances purely activated by glycine. However, functional GluN1/GluN3 receptors have not been identified in native adult tissues. We discovered that GluN1/GluN3A receptors are operational in neurons of the mouse adult medial habenula (MHb), an epithalamic area controlling aversive physiological states. In the absence of glycinergic neuronal specializations in the MHb, glial cells tuned neuronal activity via GluN1/GluN3A receptors. Reducing GluN1/GluN3A receptor levels in the MHb prevented place-aversion conditioning. Our study extends the physiological and behavioral implications of glycine by demonstrating its control of negatively valued emotional associations via excitatory glycinergic NMDA receptors.

PMID:
31601771
DOI:
10.1126/science.aax1522

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