Marcaggi Païkan
Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK,
Cerebellum. 2015 Jun;14(3):341-53. doi: 10.1007/s12311-014-0629-5.
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.
小脑皮质中1型大麻素受体（CB1）的表达显著较高，CB1是一种大麻素结合蛋白，负责大麻的精神活性作用。CB1主要存在于分子层的突触前成分中。虽然基因缺失或外源性大麻素对动物行为的影响支持了小脑CB1的功能重要性，但对急性灌流的啮齿动物小脑切片进行的体外实验为内源性大麻素在突触信号传导中的作用提供了证据。这些研究表明，内源性大麻素可由浦肯野细胞短暂释放，并在突触处以与信息传递相反的方向（逆行）发出信号。在此，在描述了小脑内源性大麻素系统的报道表达模式后，我回顾了积累的体外数据，这些数据探讨了逆行性内源性大麻素信号传导的机制，并确定2-花生四烯酸甘油酯为该信号传导的介质。讨论了导致内源性大麻素释放的机制、CB1激活的影响以及相关的突触可塑性机制，并指出了仍未解决的问题。值得注意的是，有人认为，为了理解内源性大麻素在小脑皮质中的功能，需要确定这种信号传导的空间特异性及其诱导所需的生理条件。
