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Cerebellar Endocannabinoids: Retrograde Signaling from Purkinje Cells

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Abstract

The cerebellar cortex exhibits a strikingly high expression of type 1 cannabinoid receptor (CB1), the cannabinoid binding protein responsible for the psychoactive effects of marijuana. CB1 is primarily found in presynaptic elements in the molecular layer. While the functional importance of cerebellar CB1 is supported by the effect of gene deletion or exogenous cannabinoids on animal behavior, evidence for a role of endocannabinoids in synaptic signaling is provided by in vitro experiments on superfused acute rodent cerebellar slices. These studies have demonstrated that endocannabinoids can be transiently released by Purkinje cells and signal at synapses in a direction opposite to information transfer (retrograde). Here, following a description of the reported expression pattern of the endocannabinoid system in the cerebellum, I review the accumulated in vitro data, which have addressed the mechanism of retrograde endocannabinoid signaling and identified 2-arachidonoylglycerol as the mediator of this signaling. The mechanisms leading to endocannabinoid release, the effects of CB1 activation, and the associated synaptic plasticity mechanisms are discussed and the remaining unknowns are pointed. Notably, it is argued that the spatial specificity of this signaling and the physiological conditions required for its induction need to be determined in order to understand endocannabinoid function in the cerebellar cortex.

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Acknowledgments

This work was supported by the UK Medical Research Council (Career Development Award G0600064) and the Centre National pour la Recherche Scientifique. I thank B. Barbour and J. B. Boulé for their comments on the manuscript, and M. Elphick for discussion.

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The author has no conflict of interest associated with this manuscript.

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Marcaggi, P. Cerebellar Endocannabinoids: Retrograde Signaling from Purkinje Cells. Cerebellum 14, 341–353 (2015). https://doi.org/10.1007/s12311-014-0629-5

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