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

Y. Otsu, E. Darcq, K. Pietrajtis, F. Mátyás, E. Schwartz, T. Bessaih, S. Abi Gerges, C. V. Rousseau, T. Grand, S. Dieudonné, P. Paoletti, L. Acsády, C. Agulhon, B. L. Kieffer, M. A. Diana

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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.

Original languageEnglish
Pages (from-to)250-254
Number of pages5
JournalScience
Volume366
Issue number6462
DOIs
Publication statusPublished - Oct 11 2019

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Cite this

Otsu, Y., Darcq, E., Pietrajtis, K., Mátyás, F., Schwartz, E., Bessaih, T., Abi Gerges, S., Rousseau, C. V., Grand, T., Dieudonné, S., Paoletti, P., Acsády, L., Agulhon, C., Kieffer, B. L., & Diana, M. A. (2019). Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula. Science, 366(6462), 250-254. https://doi.org/10.1126/science.aax1522