小柯机器人

Fos神经网络的双向抑制可塑性
2020-12-10 16:42

美国哈佛医学院Michael E. Greenberg研究团队的最新研究揭示了Fos神经元网络的双向渗透抑制可塑性。2020年11月9日,《自然》在线发表了这一成果。

研究人员发现,当小鼠在新环境空间中探索时,表达小白蛋白的中间神经元对Fos激活的海马CA1锥体神经元的抑制作用增强,而对表达胆囊收缩素中间神经元的抑制作用则减弱。当破坏FOS转录因子复合物的功能时,这种双向抑制作用便消失。单细胞RNA测序、核糖体相关mRNA谱分析和染色质分析与电生理学相结合表明FOS激活Scg2的转录,该基因编码多个不同的神经肽,以协调这些抑制作用的变化。由于表达小白蛋白和胆囊收缩素的中间神经元介导锥体细胞活性的特征不同,SCG2依赖性抑制突触的识别可能会影响体内网络的功能。

与此预测一致,在没有Scg2的情况下,海马γ节律和锥体细胞与θ期的偶联发生了显著改变。这些发现揭示了FOS和SCG2通过重新建立局部抑制以形成选择性调节状态在建立Fos激活神经元网络方面的决定作用。作用于不同抑制途径的相反可塑性机制可能支持随着时间推移而巩固记忆的理论。

据介绍,行为经验会激活稀疏神经元群体中的FOS转录因子,这对于编码和回忆特定事件至关重要。但是,对经验诱导脑电路重组以建立Fos激活细胞网络的机制了解有限。尚不知道在这个过程中是否需要FOS来充当最近神经活动的标记;如果是这样,那么有待探究那个Fos靶基因充当了回路重组的基石。

附:英文原文

Title: Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network

Author: Ee-Lynn Yap, Noah L. Pettit, Christopher P. Davis, M. Aurel Nagy, David A. Harmin, Emily Golden, Onur Dagliyan, Cindy Lin, Stephanie Rudolph, Nikhil Sharma, Eric C. Griffith, Christopher D. Harvey, Michael E. Greenberg

Issue&Volume: 2020-12-09

Abstract: Behavioural experiences activate the FOS transcription factor in sparse populations of neurons that are critical for encoding and recalling specific events1,2,3. However, there is limited understanding of the mechanisms by which experience drives circuit reorganization to establish a network of Fos-activated cells. It is also not known whether FOS is required in this process beyond serving as a marker of recent neural activity and, if so, which of its many gene targets underlie circuit reorganization. Here we demonstrate that when mice engage in spatial exploration of novel environments, perisomatic inhibition of Fos-activated hippocampal CA1 pyramidal neurons by parvalbumin-expressing interneurons is enhanced, whereas perisomatic inhibition by cholecystokinin-expressing interneurons is weakened. This bidirectional modulation of inhibition is abolished when the function of the FOS transcription factor complex is disrupted. Single-cell RNA-sequencing, ribosome-associated mRNA profiling and chromatin analyses, combined with electrophysiology, reveal that FOS activates the transcription of Scg2, a gene that encodes multiple distinct neuropeptides, to coordinate these changes in inhibition. As parvalbumin- and cholecystokinin-expressing interneurons mediate distinct features of pyramidal cell activity4,5,6, the SCG2-dependent reorganization of inhibitory synaptic input might be predicted to affect network function in vivo. Consistent with this prediction, hippocampal gamma rhythms and pyramidal cell coupling to theta phase are significantly altered in the absence of Scg2. These findings reveal an instructive role for FOS and SCG2 in establishing a network of Fos-activated neurons via the rewiring of local inhibition to form a selectively modulated state. The opposing plasticity mechanisms acting on distinct inhibitory pathways may support the consolidation of memories over time.

DOI: 10.1038/s41586-020-3031-0

Source: https://www.nature.com/articles/s41586-020-3031-0

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
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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