小柯机器人

英国伦敦大学学院Kenneth D. Harris、Stéphane Bugeon等研究人员合作发现，一个转录组轴可预测大脑皮层间神经元的状态调控。相关论文于2022年7月6日在线发表在《自然》杂志上。

研究人员表明初级视觉皮层（V1）的抑制性亚型与大脑状态有不同的关联，这些关联由一个单一的因素组织：沿着转录组变化的主轴的位置。研究人员将小鼠V1的体内双光子钙成像与转录组方法相结合，在体外切片中识别72个选定基因的mRNA。研究人员利用以前定义的转录组群，将1-3层的抑制性神经元成像分为5个亚类、11个类型和35个亚类的三级层次。对视觉刺激的反应仅在亚类之间有明显的不同，Sncg亚类的细胞被统一抑制，而其他亚类的细胞主要是兴奋。大脑状态的调节在所有层次上都不同，但可以从第一个转录组的主成分中大致预测出来，这也预测了与同时记录的细胞之间的相关性。

在静止、振荡脑状态下发射较多的抑制性亚型，其轴突在第1层的部分较小，脉冲较窄，输入阻抗较低，体外测定的适应性较弱，并且表达较多的抑制性胆碱能受体。在唤醒期发射较多的亚型则具有相反的特性。因此，一个简单的原则可能在很大程度上解释了不同的抑制性V1亚型是如何形成依赖状态的皮层处理的。

据了解，转录组学显示，皮层抑制性神经元表现出精细分子亚型的巨大多样性，但不知道这些亚型在活脑中是否有相应的不同活动模式。

附：英文原文

Title: A transcriptomic axis predicts state modulation of cortical interneurons

Author: Bugeon, Stphane, Duffield, Joshua, Dipoppa, Mario, Ritoux, Anne, Prankerd, Isabelle, Nicoloutsopoulos, Dimitris, Orme, David, Shinn, Maxwell, Peng, Han, Forrest, Hamish, Viduolyte, Aiste, Reddy, Charu Bai, Isogai, Yoh, Carandini, Matteo, Harris, Kenneth D.

Issue&Volume: 2022-07-06

Abstract: Transcriptomics has revealed that cortical inhibitory neurons exhibit a great diversity of fine molecular subtypes1,2,3,4,5,6, but it is not known whether these subtypes have correspondingly diverse patterns of activity in the living brain. Here we show that inhibitory subtypes in primary visual cortex (V1) have diverse correlates with brain state, which are organized by a single factor: position along the main axis of transcriptomic variation. We combined in vivo two-photon calcium imaging of mouse V1 with a transcriptomic method to identify mRNA for 72 selected genes in ex vivo slices. We classified inhibitory neurons imaged in layers 1–3 into a three-level hierarchy of 5 subclasses, 11 types and 35 subtypes using previously defined transcriptomic clusters3. Responses to visual stimuli differed significantly only between subclasses, with cells in the Sncg subclass uniformly suppressed, and cells in the other subclasses predominantly excited. Modulation by brain state differed at all hierarchical levels but could be largely predicted from the first transcriptomic principal component, which also predicted correlations with simultaneously recorded cells. Inhibitory subtypes that fired more in resting, oscillatory brain states had a smaller fraction of their axonal projections in layer 1, narrower spikes, lower input resistance and weaker adaptation as determined in vitro7, and expressed more inhibitory cholinergic receptors. Subtypes that fired more during arousal had the opposite properties. Thus, a simple principle may largely explain how diverse inhibitory V1 subtypes shape state-dependent cortical processing.

DOI: 10.1038/s41586-022-04915-7

Source: https://www.nature.com/articles/s41586-022-04915-7

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
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