Optogenetic control of striatal dopamine release in rats.
Optogenetic control of striatal dopamine release in rats.
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DOI：
10.1111/j.1471-4159.2010.06850.x
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发表时间：
2010-09-01
影响因子：
4.7
通讯作者：
Budygin EA
中科院分区：
文献类型：
--
作者：
Bass CE;Grinevich VP;Vance ZB;Sullivan RP;Bonin KD;Budygin EA
神经元放电的光遗传学控制已经成为一种越来越优雅的方法来剖析哺乳动物大脑的微电路。到目前为止，这些操作对神经递质释放的检查已经很少。在这里，我们提出了第一个深入分析的光遗传学刺激多巴胺神经传递在背侧纹状体的麻醉大鼠。通过结合光遗传学和快速扫描循环伏安法的紧密空间和时间分辨率，我们确定了控制大鼠体内背侧纹状体中阶段性多巴胺释放所需的参数。光学诱导多巴胺释放的动力学镜像建立了电诱发释放的模型，表明电刺激对离子通道和多巴胺转运蛋白的潜在伪影可以忽略不计。此外，细胞外pH值没有变化表明光学刺激不会改变血流。多巴胺释放的光学控制是高度可重复和灵活的。我们能够反复诱发多巴胺释放浓度小至单个多巴胺瞬变（50 nM）。存在U形频率响应曲线，其中最大刺激诱导多巴胺流出超过500 nM。总之，这些结果对于理解多巴胺能障碍的神经生物学基础具有明显的意义，并提供了有效操纵多巴胺模式的框架。
Optogenetic control over neuronal firing has become an increasingly elegant method to dissect the microcircuitry of mammalian brains. To date, examination of these manipulations on neurotransmitter release has been minimal. Here we present the first in-depth analysis of optogenetic stimulation on dopamine neurotransmission in the dorsal striatum of urethane-anesthetized rats. By combining the tight spatial and temporal resolution of both optogenetics and fast-scan cyclic voltammetry we have determined the parameters necessary to control phasic dopamine release in the dorsal striatum of rats in vivo. The kinetics of optically induced dopamine release mirror established models of electrically evoked release, indicating that potential artifacts of electrical stimulation on ion channels and the dopamine transporter are negligible. Furthermore a lack of change in extracellular pH indicates that optical stimulation does not alter blood flow. Optical control over dopamine release is highly reproducible and flexible. We are able to repeatedly evoke concentrations of dopamine release as small as a single dopamine transient (50 nM). A U-shaped frequency response curve exists with maximal stimulation inducing dopamine effluxes exceeding 500 nM. Taken together, these results have obvious implications for understanding the neurobiological basis of dopaminergic-based disorders and provide the framework to effectively manipulate dopamine patterns.
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影响因子：
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通讯作者：
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影响因子：
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