美国耶鲁大学医学院Michael J. Higley、Michael C. Crair等研究人员合作实现了对皮层回路神经元活动的同时介观和双光子成像。该研究成果于2019年11月4日在线发表于国际学术期刊《自然—方法学》杂志。

研究人员提出了一种方法，可用于同时对局部微电路进行细胞分辨率的双光子钙成像和在清醒的小鼠中整个皮层的介观宽视野钙成像。这一多尺度方法包括具有正交轴设计的显微镜，其中介观物镜位于大脑上方，而双光子物镜则位于水平方向，并通过微棱镜进行成像。研究人员还介绍了一种病毒转导方法，可在小鼠大脑中稳定而广泛地传递基因。这些方法使研究人员能够识别具有远距离皮层网络的锥体神经元和表达血管活性肠肽的中间神经元的行为依赖状态的功能连接。这个成像系统为研究各种空间尺度上的皮质结构提供了强大的方案。

据了解，自发和感觉诱发的活动在哺乳动物皮质的不同空间尺度上传播，但是技术挑战限制了局部神经元回路功能与大脑范围网络动力学之间的概念联系。

附：英文原文

Title: Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits

Author: Daniel Barson, Ali S. Hamodi, Xilin Shen, Gyorgy Lur, R. Todd Constable, Jessica A. Cardin, Michael C. Crair, Michael J. Higley

Issue&Volume: 2019-11-04

Abstract: Spontaneous and sensory-evoked activity propagates across varying spatial scales in the mammalian cortex, but technical challenges have limited conceptual links between the function of local neuronal circuits and brain-wide network dynamics. We present a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake mice. Our multi-scale approach involves a microscope with an orthogonal axis design where the mesoscopic objective is oriented above the brain and the two-photon objective is oriented horizontally, with imaging performed through a microprism. We also introduce a viral transduction method for robust and widespread gene delivery in the mouse brain. These approaches allow us to identify the behavioral state-dependent functional connectivity of pyramidal neurons and vasoactive intestinal peptide-expressing interneurons with long-range cortical networks. Our imaging system provides a powerful strategy for investigating cortical architecture across a wide range of spatial scales.

DOI: 10.1038/s41592-019-0625-2

Source: https://www.nature.com/articles/s41592-019-0625-2