Faculty Collaboration Database

Coordinated regulation of endocannabinoid-mediated retrograde synaptic suppression in the cerebellum by neuronal and astrocytic monoacylglycerol lipase. Sci Rep 2016 Oct 24;6:35829

Date

10/25/2016

Pubmed ID

27775008

Pubmed Central ID

PMC5075776

DOI

10.1038/srep35829

Scopus ID

2-s2.0-84992364810 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

The endocannabinoid 2-arachidonoylglycerol (2-AG) mediates retrograde synaptic depression including depolarization-induced suppression of excitation (DSE) and inhibition (DSI). 2-AG is degraded primarily by monoacylglycerol lipase (MAGL), which is expressed in neurons and astrocytes. Using knockout mice in which MAGL is deleted globally or selectively in neurons or astrocytes, we investigated the relative contribution of neuronal and astrocytic MAGL to the termination of DSE and DSI in Purkinje cells (PCs) in cerebellar slices. We report that neuronal MAGL plays a predominant role in terminating DSE at climbing fiber (CF) to PC synapses, while both neuronal and astrocytic MAGL significantly contributes to the termination of DSE at parallel fiber (PF) to PC synapses and DSI at putative Stellate cell to PC synapses. Thus, DSE and DSI at different synapses is not uniformly affected by global and cell type-specific knockout of MAGL. Additionally, MAGL global knockout, but not cell type-specific knockout, caused tonic activation and partial desensitization of the CB₁ receptor at PF-PC synapses. This tonic CB₁ activation is mediated by 2-AG since it was blocked by the diacylglycerol lipase inhibitor DO34. Together, these results suggest that both neuronal and astrocytic MAGL contribute to 2-AG clearance and prevent CB₁ receptor over-stimulation in the cerebellum.

Author List

Liu X, Chen Y, Vickstrom CR, Li Y, Viader A, Cravatt BF, Liu QS

Author

Qing-song Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Arachidonic Acids
Astrocytes
Benzodioxoles
Benzoxazines
Cerebellum
Endocannabinoids
Enzyme Inhibitors
Female
Glycerides
Male
Mice, Knockout
Monoacylglycerol Lipases
Morpholines
Naphthalenes
Neurons
Patch-Clamp Techniques
Piperidines
Purkinje Cells
Receptor, Cannabinoid, CB1
Synapses