Optogenetic reactivation of prefrontal social neural ensembles mimics social buffering of fear
Optogenetic reactivation of prefrontal social neural ensembles mimics social buffering of fear
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DOI：
10.1038/s41386-020-0631-1
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发表时间：
2020-02-08
影响因子：
7.6
通讯作者：
Donaldson, Zoe R.
中科院分区：
文献类型：
--
作者：
Gutzeit, Vanessa A.;Ahuna, Kylia;Donaldson, Zoe R.
当同伴的存在减弱了压力或恐惧引发事件的生理和/或行为影响时，就会发生社会缓冲。它代表了一种社会互动可以立即有效地调节行为的方式。因此，社会缓冲是一种机制，通过这种机制，强大的社会支持可以提高对精神疾病的抵抗力。虽然社会缓冲的行为和神经内分泌影响在包括人类在内的多个物种中得到了很好的研究，但这种行为现象的神经基础在很大程度上仍未被探索。先前的研究表明，边缘下前额叶皮层（IL-PFC）对处理社会信息很重要，在单独的研究中，对调节恐惧和焦虑也很重要。因此，我们假设IL-PFC内的社交活跃细胞可以整合社交信息来调节恐惧反应。为了验证这一假设，我们在雄性和雌性小鼠中采用了社会缓冲范式。与之前对大鼠的研究类似，我们发现，在引起恐惧和焦虑的环境中，caglavin的存在减少了冻结。根据以前的工作，我们表明，与一个新的或熟悉的同种诱导活性的IL-PFC的即时早期基因（IEG）的表达增加所证明的。然后，我们利用活性依赖性标记小鼠系ArcCreER（T2）小鼠，在新cagliptin的社会编码过程中活跃的神经元中表达通道视紫红质（ChR 2）。我们发现，这些社会活动神经元集合的光遗传学再激活表型模仿了在学习和先天恐惧背景下雄性和雌性小鼠中cagglutamine存在的影响，而不是固有的奖励或改变运动。这些数据表明，在IL-PFC的社会神经合奏可能有助于社会缓冲的恐惧。这些神经元可能代表恐惧和焦虑症的新治疗靶点。
Social buffering occurs when the presence of a companion attenuates the physiological and/or behavioral effects of a stressful or fear-provoking event. It represents a way in which social interactions can immediately and potently modulate behavior. As such, social buffering is one mechanism by which strong social support increases resilience to mental illness. Although the behavioral and neuroendocrine impacts of social buffering are well studied in multiple species, including humans, the neuronal underpinnings of this behavioral phenomenon remain largely unexplored. Previous work has shown that the infralimbic prefrontal cortex (IL-PFC) is important for processing social information and, in separate studies, for modulating fear and anxiety. Thus, we hypothesized that socially active cells within the IL-PFC may integrate social information to modulate fear responsivity. To test this hypothesis, we employed social buffering paradigms in male and female mice. Similar to prior studies in rats, we found that the presence of a cagemate reduced freezing in fear- and anxiety-provoking contexts. In accordance with previous work, we demonstrated that interaction with a novel or familiar conspecific induces activity in the IL-PFC as evidenced by increased immediate early gene (IEG) expression. We then utilized an activity-dependent tagging murine line, the ArcCreER(T2) mice, to express channelrhodopsin (ChR2) in neurons active during the social encoding of a new cagemate. We found that optogenetic reactivation of these socially active neuronal ensembles phenocopied the effects of cagemate presence in male and female mice in learned and innate fear contexts without being inherently rewarding or altering locomotion. These data suggest that a social neural ensemble within the IL-PFC may contribute to social buffering of fear. These neurons may represent a novel therapeutic target for fear and anxiety disorders.