Chemogenetic activation of oxytocin neurons: Temporal dynamics, hormonal release, and behavioral consequences
Chemogenetic activation of oxytocin neurons: Temporal dynamics, hormonal release, and behavioral consequences
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DOI：
10.1016/j.psyneuen.2019.03.019
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发表时间：
2019-08-01
影响因子：
3.7
通讯作者：
Grinevich, Valery
中科院分区：
文献类型：
--
作者：
Grund, Thomas;Tang, Yan;Grinevich, Valery
化学遗传学提供对神经元活动的特定细胞类型的远程控制。在这里，我们描述了用于特异性激活催产素(OT)神经元的化学遗传学的应用，作为一类独特的神经内分泌细胞的代表。我们将重组腺相关载体注射到大鼠下丘脑中，驱动修饰的人M受体的刺激性亚单位hM3Dq在OT神经元中实现细胞类型特异性表达。由于OT神经元的化学激活作用尚未见报道，我们通过监测OT神经元的钙波动，以及OT在脑内和外周的释放，系统地分析了OT神经元在活体内反应的时间动力学。我们进一步在行为水平上为化学发生操作的有效性提供了证据，证明了OT神经元的诱发激活导致了社会动机和焦虑的缓解。总之，我们的结果将对从事神经内分泌系统生理学、行为的肽能调节和翻译精神病学的研究人员有所裨益。
Chemogenetics provides cell type-specific remote control of neuronal activity. Here, we describe the application of chemogenetics used to specifically activate oxytocin (OT) neurons as representatives of a unique class of neuroendocrine cells. We injected recombinant adeno-associated vectors, driving the stimulatory subunit hM3Dq of a modified human muscarinic receptor into the rat hypothalamus to achieve cell type-specific expression in OT neurons. As chemogenetic activation of OT neurons has not been reported, we provide systematic analysis of the temporal dynamics of OT neuronal responses in vivo by monitoring calcium fluctuations in OT neurons, and intracerebral as well as peripheral release of OT. We further provide evidence for the efficiency of chemogenetic manipulation at behavioral levels, demonstrating that evoked activation of OT neurons leads to social motivation and anxiolysis. Altogether, our results will be profitable for researchers working on the physiology of neuroendocrine systems, peptidergic modulation of behaviors and translational psychiatry.