A Fear Memory Engram and Its Plasticity in the Hypothalamic Oxytocin System
A Fear Memory Engram and Its Plasticity in the Hypothalamic Oxytocin System
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DOI：
10.1016/j.neuron.2019.04.029
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发表时间：
2019-07-03
期刊：
影响因子：
16.2
通讯作者：
Grinevich, Valery
中科院分区：
文献类型：
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作者：
Hasan, Mazahir T.;Althammer, Ferdinand;Grinevich, Valery
催产素（OT）释放轴突终末到中央杏仁核发挥抗焦虑作用。为了研究OT神经元的哪个亚群有助于这种效应，我们开发了一种新的方法：病毒递送的遗传活性诱导的细胞系综标记（vGATE）。使用vGATE方法，我们鉴定并永久标记了OT细胞的一小部分亚群，其通过光遗传学刺激强烈减弱了情境恐惧诱导的冻结，并且标记的OT神经元的药物遗传学沉默损害了情境特异性恐惧消退，这表明标记的OT神经元分别是控制情境恐惧的足够和必要的。有趣的是，经历过恐惧的大鼠的OT细胞末梢在杏仁核中显示出增强的谷氨酸释放。此外，暴露于另一轮恐惧条件反射的大鼠在新环境中显示出比熟悉环境多5倍的激活大细胞OT神经元，这可能是由于普遍的恐惧反应。因此，我们的研究结果提供了第一个证据表明，下丘脑OT神经元代表恐惧记忆痕迹。
Oxytocin (OT) release by axonal terminals onto the central nucleus of the amygdala exerts anxiolysis. To investigate which subpopulation of OT neurons contributes to this effect, we developed a novel method: virus-delivered genetic activity-induced tagging of cell ensembles (vGATE). With the vGATE method, we identified and permanently tagged a small subpopulation of OT cells, which, by optogenetic stimulation, strongly attenuated contextual fear-induced freezing, and pharmacogenetic silencing of tagged OT neurons impaired context-specific fear extinction, demonstrating that the tagged OT neurons are sufficient and necessary, respectively, to control contextual fear. Intriguingly, OT cell terminals of fear-experienced rats displayed enhanced glutamate release in the amygdala. Furthermore, rats exposed to another round of fear conditioning displayed 5-fold more activated magnocellular OT neurons in a novel environment than a familiar one, possibly for a generalized fear response. Thus, our results provide first evidence that hypothalamic OT neurons represent a fear memory engram.