Fast Phasic Release Properties of Dopamine Studied with a Channel Biosensor
Fast Phasic Release Properties of Dopamine Studied with a Channel Biosensor
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DOI：
10.1523/jneurosci.2355-14.2014
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发表时间：
2014-08-27
影响因子：
5.3
通讯作者：
Mennerick, Steven
中科院分区：
文献类型：
--
作者：
Kress, Geraldine J.;Shu, Hong-Jin;Mennerick, Steven
很少有其他神经递质像多巴胺那样引起神经精神病学和神经病学的强烈兴趣，但现有的监测多巴胺释放的技术在我们的理解中留下了重要的时空差距。电化学和荧光成像工具的开发填补了这一空白，但这些方法具有重要的局限性。我们通过将多巴胺门控氯离子通道引入大鼠背侧纹状体中等棘神经元（强多巴胺神经支配的目标）来规避这些限制，从而将多巴胺从慢速递质转变为快速递质，并揭示了研究多巴胺释放的即时调节的新机会。我们展示了该通道的药理学和生物物理特性，使其适合快速、局部多巴胺测量，并且我们首次展示了对背侧纹状体中囊泡多巴胺释放的自发反应和诱发反应。诱发的多巴胺电流分为快速的单突触成分和由烟碱受体激活介导的缓慢上升和衰减的双突触成分。总之，LGC-53 代表了一种多巴胺生物传感器，其特性适合于多巴胺神经支配目标中不同多巴胺信号的时间分离。
Few other neurotransmitters are of as intense interest to neuropsychiatry and neurology as dopamine, yet existing techniques to monitor dopamine release leave an important spatiotemporal gap in our understanding. Electrochemistry and fluorescence imaging tools have been developed to fill the gap, but these methods have important limitations. We circumvent these limitations by introducing a dopamine-gated chloride channel into rat dorsal striatal medium spiny neurons, targets of strong dopamine innervation, thereby transforming dopamine from a slow transmitter into a fast transmitter and revealing new opportunities for studying moment-to-moment regulation of dopamine release. We demonstrate pharmacological and biophysical properties of the channel that make it suitable for fast, local dopamine measurements, and we demonstrate for the first time spontaneous and evoked responses to vesicular dopamine release in the dorsal striatum. Evoked dopamine currents were separated into a fast, monosynaptic component and a slower-rising and decaying disynaptic component mediated by nicotinic receptor activation. In summary, LGC-53 represents a dopamine biosensor with properties suitable for temporal separation of distinct dopamine signals in targets of dopamine innervation.