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The Journal of Neuroscience, 2001, 21:RC188:1-5

RAPID COMMUNICATION
Metabotropic Glutamate Receptors Drive the Endocannabinoid System in Hippocampus

Namita Varma¹, Gregory C. Carlson¹, Catherine Ledent², and Bradley E. Alger¹

¹ Department of Physiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201, and ² Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucléaire, Université libre de Bruxelles, B-1070 Brussels, Belgium

Endocannabinoids are key intercellular signaling molecules in the brain, but the physiological regulation of the endocannabinoid system is not understood. We used the retrograde signal process called depolarization-induced suppression of inhibition (DSI) to study the regulation of this system. DSI is produced when an endocannabinoid released from pyramidal cells suppresses IPSCs by activating CB1R cannabinoid receptors located on inhibitory interneurons. We now report that activation of group I metabotropic glutamate receptors (mGluRs) enhances DSI and that this effect is blocked by antagonists of both mGluRs and of CB1R. We also found that DSI is absent in CB1R knock-out (CB1R^/) mice, and, strikingly, that mGluR agonists have no effect on IPSCs in these mice. We conclude that group I mGluR-induced enhancement of DSI, and suppression of IPSCs, is actually mediated by endocannabinoids. This surprising result opens up new approaches to the investigation of cannabinoid actions in the brain.

Key words: DSI; IPSCs; retrograde; transmitter release; cannabinoid; CB1; mGluR; CA1; presynaptic; disinhibition

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Copyright © Society for Neuroscience  0270-6474//$05.00/0

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