Division of Health Science, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Neuroscientist. 2012 Apr;18(2):119-32. doi: 10.1177/1073858410397377. Epub 2011 Apr 29.
Since the first reports of endocannabinoid-mediated retrograde signaling in 2001, great advances have been made toward understanding the molecular basis and functions of the endocannabinoid system. Electrophysiological studies have revealed that the endocannabinoid system is functional at various types of synapses throughout the brain. Basic mechanisms have been clarified as to how endocannabinoids are produced and released from postsynaptic neurons and regulate neurotransmitter release through activating presynaptic cannabinoid CB(1) receptors, although there remain unsolved questions and some discrepancies. In addition to this major function, recent studies suggest diverse functions of endocannabinoids, including control of other endocannabinoid-independent forms of synaptic plasticity, regulation of neuronal excitability, stimulation of glia-neuron interaction, and induction of CB(1)R-independent plasticity. Using recently developed pharmacological and genetic tools, behavioral studies have elucidated the roles of the endocannabinoid system in various aspects of neural functions. In this review, we make a brief overview of molecular mechanisms underlying the endocannabinoid-mediated synaptic modulation and also summarize recent findings, which shed new light on a diversity of functional roles of endocannabinoids.
自 2001 年首次报道内源性大麻素介导的逆行信号以来，人们在理解内源性大麻素系统的分子基础和功能方面取得了重大进展。电生理学研究表明，内源性大麻素系统在大脑中的各种类型突触中均具有功能。已经阐明了内源性大麻素如何从突触后神经元中产生和释放，并通过激活突触前大麻素 CB1 受体来调节神经递质释放的基本机制，尽管仍存在未解决的问题和一些差异。除了这种主要功能外，最近的研究还表明内源性大麻素具有多种功能，包括控制其他内源性大麻素独立形式的突触可塑性、调节神经元兴奋性、刺激神经胶质-神经元相互作用以及诱导 CB1R 独立的可塑性。使用最近开发的药理学和遗传学工具，行为研究阐明了内源性大麻素系统在神经功能各个方面的作用。在这篇综述中，我们简要概述了内源性大麻素介导的突触调节的分子机制，并总结了最近的发现，这些发现为内源性大麻素的多种功能作用提供了新的认识。
