生物谷综合:2007年56卷第6期《神经元》的封面是几条金鱼在背景为大麻叶的花瓶中漫游的蒙太奇照片。这张照片对应的文章是Cachope等报道的关于大麻中的成分内大麻素具有介导增强突触传递作用的研究。
此前的研究表明,大麻醇I型受体的突触前激活作用表明大麻中的内大麻素是突触传递的化学抑制剂。然而,Cachope小组的研究结果否认了这一观点,他们发现内大麻素的分散释放能够从电与化学两方面混合增强Mauthner金鱼细胞的突触传递。
更值得注意的是,这种增强作用并非只限于突触响应的谷氨酸盐成分,而且还包括相应的电传递的增强。研究表明,这种作用涉及大麻醇I型受体的活化,以及通过附近的静脉曲张释放多巴胺进行间接介导,接着再通过环磷酸腺苷依赖型蛋白激酶介导突触的方式增强突触反应。因此,内大麻素的释放具有明显增强突触传递的作用,其功能包括调节间隙连接介导电突触。
研究人员认为,类似的内大麻素与多巴胺系统的相互作用可能分布广泛,而其它大麻衍生物的潜在作用也值得进一步研究。(武彦文/编译)
原始出处:
Neuron, Vol 56, 1034-1047, 20 December 2007
Article
Potentiation of Electrical and Chemical Synaptic Transmission Mediated by Endocannabinoids
Roger Cachope,1 Ken Mackie,2 Antoine Triller,3 John O'Brien,4 and Alberto E. Pereda1,
1 Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2 Department of Anesthesiology, University of Washington, Seattle, WA 98195, USA
3 Ecole Normale Superieure, Paris, France
4 University of Texas Health Science Center, Houston, TX 77030, USA
Corresponding author
Alberto E. Pereda
apereda@aecom.yu.edu
Summary
Endocannabinoids are well established as inhibitors of chemical synaptic transmission via presynaptic activation of the cannabinoid type 1 receptor (CB1R). Contrasting this notion, we show that dendritic release of endocannabinoids mediates potentiation of synaptic transmission at mixed (electrical and chemical) synaptic contacts on the goldfish Mauthner cell. Remarkably, the observed enhancement was not restricted to the glutamatergic component of the synaptic response but also included a parallel increase in electrical transmission. This effect involved the activation of CB1 receptors and was indirectly mediated via the release of dopamine from nearby varicosities, which in turn led to potentiation of the synaptic response via a cAMP-dependent protein kinase-mediated postsynaptic mechanism. Thus, endocannabinoid release can potentiate synaptic transmission, and its functional roles include the regulation of gap junction-mediated electrical synapses. Similar interactions between endocannabinoid and dopaminergic systems may be widespread and potentially relevant for the motor and rewarding effects of cannabis derivatives.