美国波士顿大学Xue Han和麻省理工学院Edward S. Boyden等研究人员，利用遗传编码的电压探针实现了对清醒活动小鼠的神经活动进行群体成像。该项研究成果于2019年10月9日在线发表于《自然》杂志。

研究人员研发了一种遗传编码的荧光电压探针叫做SomArchon，它具有毫秒级的响应时间，并且与光遗传学控制兼容，并且可以提高灵敏度、信噪比，并且可观察到的神经元数量是以前发表的完全遗传方法编码探针的数倍。在常规的单光子显微镜下，SomArchon可以一次对头部固定的、醒着的、活动的小鼠的多个大脑区域（皮质、海马和纹状体）同时进行大约13个神经元的常规群体分析。使用SomArchon，研究人员可以检测到运动过程中纹状体神经元的正反应和负反应，如同之前通过电生理学报道的那样，但使用现代钙成像技术不容易检测到，这突显了电压成像的力量，并揭示了双向调节模式。

研究人员还测试了脉冲与单个海马神经元的亚阈值θ振荡之间的关系，SomArchon显示，与其自身的亚阈值θ振荡相比，局部场电势θ振荡的单个神经元脉冲存在更多锁相。因此，SomArchon报告了清醒、活动小鼠中的脉冲和阈下电压动态。

据介绍，神经科学的一个长期目标正是在清醒、活动的哺乳动物中对不同的神经元群体进行膜电压成像。

附：英文原文

Title: Population imaging of neural activity in awake behaving mice

Author: Kiryl D. Piatkevich, Seth Bensussen, Hua-an Tseng, Sanaya N. Shroff, Violeta Gisselle Lopez-Huerta, Demian Park, Erica E. Jung, Or A. Shemesh, Christoph Straub, Howard J. Gritton, Michael F. Romano, Emma Costa, Bernardo L. Sabatini, Zhanyan Fu, Edward S. Boyden, Xue Han

Issue&Volume: 2019-10-09

Abstract: 

A longstanding goal in neuroscience has been to image membrane voltage across a population of individual neurons in an awake, behaving mammal. Here we describe a genetically encoded fluorescent voltage indicator, SomArchon, which exhibits millisecond response times and is compatible with optogenetic control, and which increases the sensitivity, signal-to-noise ratio, and number of neurons observable several-fold over previously published fully genetically encoded reagents1,2,3,4,5,6,7,8. Under conventional one-photon microscopy, SomArchon enables the routine population analysis of around 13 neurons at once, in multiple brain regions (cortex, hippocampus, and striatum) of head-fixed, awake, behaving mice. Using SomArchon, we detected both positive and negative responses of striatal neurons during movement, as previously reported by electrophysiology but not easily detected using modern calcium imaging techniques9,10,11, highlighting the power of voltage imaging to reveal bidirectional modulation. We also examined how spikes relate to the subthreshold theta oscillations of individual hippocampal neurons, with SomArchon showing that the spikes of individual neurons are more phase-locked to their own subthreshold theta oscillations than to local field potential theta oscillations. Thus, SomArchon reports both spikes and subthreshold voltage dynamics in awake, behaving mice.

DOI: 10.1038/s41586-019-1641-1

Source: https://www.nature.com/articles/s41586-019-1641-1