Neuronal and Astrocytic Monoacylglycerol Lipase Limit the Spread of Endocannabinoid Signaling in the Cerebellum. eNeuro 2016;3(3)
Date
05/18/2016Pubmed ID
27182552Pubmed Central ID
PMC4865651DOI
10.1523/ENEURO.0048-16.2016Scopus ID
2-s2.0-84992422751 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
Endocannabinoids are diffusible lipophilic molecules that may spread to neighboring synapses. Monoacylglycerol lipase (MAGL) is the principal enzyme that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG). Using knock-out mice in which MAGL is deleted globally or selectively in neurons and astrocytes, we investigated the extent to which neuronal and astrocytic MAGL limit the spread of 2-AG-mediated retrograde synaptic depression in cerebellar slices. A brief tetanic stimulation of parallel fibers in the molecular layer induced synaptically evoked suppression of excitation (SSE) in Purkinje cells, and both neuronal and astrocytic MAGL contribute to the termination of this form of endocannabinoid-mediated synaptic depression. The spread of SSE among Purkinje cells occurred only after global knock-out of MAGL or pharmacological blockade of either MAGL or glutamate uptake, but no spread was detected following neuron- or astrocyte-specific deletion of MAGL. The spread of endocannabinoid signaling was also influenced by the spatial pattern of synaptic stimulation, because it did not occur at spatially dispersed parallel fiber synapses induced by stimulating the granular layer. The tetanic stimulation of parallel fibers did not induce endocannabinoid-mediated synaptic suppression in Golgi cells even after disruption of MAGL and glutamate uptake, suggesting that heightened release of 2-AG by Purkinje cells does not spread the retrograde signal to parallel fibers that innervate Golgi cells. These results suggest that both neuronal and astrocytic MAGL limit the spatial diffusion of 2-AG and confer synapse-specificity of endocannabinoid signaling.
Author List
Chen Y, Liu X, Vickstrom CR, Liu MJ, Zhao L, Viader A, Cravatt BF, Liu QSAuthor
Qing-song Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid Transport System X-AGAnimals
Arachidonic Acids
Astrocytes
Cannabinoid Receptor Agonists
Cerebellum
Endocannabinoids
Glutamic Acid
Glycerides
Membrane Potentials
Mice, Knockout
Monoacylglycerol Lipases
Neurons
Patch-Clamp Techniques
Synaptic Transmission
Tissue Culture Techniques
