Potentiation of electrical and chemical synaptic transmission mediated by endocannabinoids
Potentiation of electrical and chemical synaptic transmission mediated by endocannabinoids
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DOI：
10.1016/j.neuron.2007.11.014
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发表时间：
2007-12-20
期刊：
影响因子：
16.2
通讯作者：
Pereda, Alberto E.
中科院分区：
文献类型：
--
作者：
Cachope, Roger;Mackie, Ken;Pereda, Alberto E.
内源性大麻素被公认为通过大麻素1型受体（CB1R）的突触前激活的化学突触传递的抑制剂。对比这一概念，我们发现，树突状释放内源性大麻素介导增强突触传递在混合（电气和化学）突触接触金鱼Mauthner细胞。值得注意的是，观察到的增强不仅限于突触反应的突触能成分，还包括电传递的平行增加。这种效应涉及CB1受体的激活，并通过附近静脉曲张释放多巴胺间接介导，这反过来又导致通过cAMP依赖性蛋白激酶介导的突触后机制增强突触反应。因此，内源性大麻素释放可以增强突触传递，其功能作用包括调节间隙连接介导的电突触。内源性大麻素和多巴胺能系统之间的类似相互作用可能是广泛的，并可能与大麻衍生物的运动和奖励作用有关。
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.