Population imaging of neural activity in awake behaving mice
Population imaging of neural activity in awake behaving mice
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DOI：
10.1038/s41586-019-1641-1
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发表时间：
2019-10-17
期刊：
影响因子：
64.8
通讯作者：
Han, Xue
中科院分区：
文献类型：
--
作者：
Piatkevich, Kiryl D.;Bensussen, Seth;Han, Xue
神经科学的一个长期目标是对清醒、有行为能力的哺乳动物的单个神经元群体的膜电压进行成像。在这里，我们描述了一种基因编码荧光电压指示器 SomArchon，它具有毫秒响应时间并且与光遗传学控制兼容，并且与之前发表的完全基因编码试剂相比，其灵敏度、信噪比和可观察的神经元数量提高了数倍 (1-8)。在传统的单光子显微镜下，SomaArchon 能够同时对头部固定、清醒、行为正常的小鼠的多个大脑区域（皮层、海马体和纹状体）中的约 13 个神经元进行常规群体分析。使用 SomArchon，我们检测到纹状体神经元在运动过程中的正向和负向反应，正如之前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 (9-11)，这凸显了电压成像揭示双向调制的能力。我们还研究了尖峰与单个海马神经元的阈下 theta 振荡的关系，SomaArchon 表明，单个神经元的尖峰与其自身的阈下 theta 振荡比局部场电位 theta 振荡更锁相。因此，SomaArchon 报告了清醒、有行为的小鼠的峰值和亚阈值电压动态。
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 reagents(1-8). 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 techniques(9-11), 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.