小柯机器人

刺激特异性下丘脑编码持续防御状态
2020-09-18 13:59

美国加州理工学院的David J. Anderson团队取得最新进展。他们发现刺激特异性下丘脑编码持续防御状态。该研究于2020年9月16日发表于国际一流学术期刊《自然》杂志上。

他们报道对自然威胁刺激的响应,小鼠中的VMHdmSF1神经元表现出持续数十秒的活动。这种持久性活动与在露天试验中的持久防御行为相关,也是持久性防御行为所必需的,并且取决于从VMHdmSF1神经元释放的神经递质。急性切片中的刺激和钙成像显示,VMHdmSF1神经元之间存在局部兴奋性连接。内窥镜对VMHdmSF1神经元的钙成像显示,群体水平的持续活动反映了单个细胞之间的异质动态。

出乎意料的是,不同但重叠的VMHdmSF1亚群被威胁性刺激的不同方式持续激活。计算模型表明,单独的复发性兴奋剂和缓慢作用的神经调节剂都不能解释维持刺激特性的持续活动。他们的结果表明,下丘脑中特定于刺激的慢速神经动力学,其时间尺度比皮质中的工作记忆要长几个数量级,有助于持久的情绪状态。

据悉,皮层、海马和运动网络中持续的神经活动已被描述为介导短暂遇到的刺激的工作记忆。暴露于刺激性刺激后,内部情绪状态(例如恐惧)也会持续存在,但尚不清楚该过程是否涉及缓慢的神经动力学。表达核受体蛋白NR5A1(也称为SF1)的腹膜下丘脑(VMHdm / c)背侧和中部的神经元对于小鼠对捕食者的防御反应是必需的。这些神经元的光遗传激活(这里称为VMHdmSF1神经元)引起的防御行为比刺激持续的时间长,这表明诱发了恐惧或焦虑的持续内部状态。

附:英文原文

Title: Stimulus-specific hypothalamic encoding of a persistent defensive state

Author: Ann Kennedy, Prabhat S. Kunwar, Ling-yun Li, Stefanos Stagkourakis, Daniel A. Wagenaar, David J. Anderson

Issue&Volume: 2020-09-16

Abstract: Persistent neural activity in cortical, hippocampal, and motor networks has been described as mediating working memory for transiently encountered stimuli1,2. Internal emotional states, such as fear, also persist following exposure to an inciting stimulus3, but it is unclear whether slow neural dynamics are involved in this process. Neurons in the dorsomedial and central subdivisions of the ventromedial hypothalamus (VMHdm/c) that express the nuclear receptor protein NR5A1 (also known as SF1) are necessary for defensive responses to predators in mice4,5,6,7. Optogenetic activation of these neurons, referred to here as VMHdmSF1 neurons, elicits defensive behaviours that outlast stimulation5,8, which suggests the induction of a persistent internal state of fear or anxiety. Here we show that in response to naturalistic threatening stimuli, VMHdmSF1 neurons in mice exhibit activity that lasts for many tens of seconds. This persistent activity was correlated with, and required for, persistent defensive behaviour in an open-field assay, and depended on neurotransmitter release from VMHdmSF1 neurons. Stimulation and calcium imaging in acute slices showed that there is local excitatory connectivity between VMHdmSF1 neurons. Microendoscopic calcium imaging of VMHdmSF1 neurons revealed that persistent activity at the population level reflects heterogeneous dynamics among individual cells. Unexpectedly, distinct but overlapping VMHdmSF1 subpopulations were persistently activated by different modalities of threatening stimulus. Computational modelling suggests that neither recurrent excitation nor slow-acting neuromodulators alone can account for persistent activity that maintains stimulus identity. Our results show that stimulus-specific slow neural dynamics in the hypothalamus, on a time scale orders of magnitude longer than that of working memory in the cortex9,10, contribute to a persistent emotional state.

DOI: 10.1038/s41586-020-2728-4

Source: https://www.nature.com/articles/s41586-020-2728-4

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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