Evoked Axonal Oxytocin Release in the Central Amygdala Attenuates Fear Response
Evoked Axonal Oxytocin Release in the Central Amygdala Attenuates Fear Response
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DOI：
10.1016/j.neuron.2011.11.030
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发表时间：
2012-02-09
期刊：
影响因子：
16.2
通讯作者：
Grinevicht, Valery
中科院分区：
文献类型：
--
作者：
Knobloch, H. Sophie;Charlet, Alexandre;Grinevicht, Valery
控制分娩和哺乳的下丘脑神经肽催产素（OT）因其对社会行为的影响而受到越来越多的关注，但它如何到达中枢脑区仍不清楚。本研究通过重组病毒获得了下丘脑OT神经元的选择性遗传通路，并通过光遗传学手段研究其连接性和调控其活性。我们发现下丘脑OT神经元的轴突在大多数前脑区域，包括中央杏仁核（CeA），一个结构，关键参与OT介导的恐惧抑制。在体外，暴露于蓝光的通道视紫红质-2-表达OT轴突激活了本地GABA能电路，抑制神经元的输出区域的CeA。值得注意的是，在体内，局部蓝光诱导的内源性OT释放强烈降低恐惧条件大鼠的冻结反应。因此，我们的研究结果表明，广泛的下丘脑OT神经元的中枢投射，并证明OT释放局部轴突末梢可以专门控制区域相关的行为。
The hypothalamic neuropeptide oxytocin (OT), which controls childbirth and lactation, receives increasing attention for its effects on social behaviors, but how it reaches central brain regions is still unclear. Here we gained by recombinant viruses selective genetic access to hypothalamic OT neurons to study their connectivity and control their activity by optogenetic means. We found axons of hypothalamic OT neurons in the majority of forebrain regions, including the central amygdala (CeA), a structure critically involved in OT-mediated fear suppression. In vitro, exposure to blue light of channelrhodopsin-2-expressing OT axons activated a local GABAergic circuit that inhibited neurons in the output region of the CeA. Remarkably, in vivo, local blue-light-induced endogenous OT release robustly decreased freezing responses in fear-conditioned rats. Our results thus show widespread central projections of hypothalamic OT neurons and demonstrate that OT release from local axonal endings can specifically control region-associated behaviors.