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一种用于在自由活动小鼠中同时进行模式化光遗传学刺激和钙成像的单光子内窥镜。

A one-photon endoscope for simultaneous patterned optogenetic stimulation and calcium imaging in freely behaving mice.

作者信息

Zhang Jinyong, Hughes Ryan N, Kim Namsoo, Fallon Isabella P, Bakhurin Konstantin, Kim Jiwon, Severino Francesco Paolo Ulloa, Yin Henry H

机构信息

Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.

Department of Neurobiology, Duke University School of Medicine, Durham, NC, USA.

出版信息

Nat Biomed Eng. 2023 Apr;7(4):499-510. doi: 10.1038/s41551-022-00920-3. Epub 2022 Aug 15.

DOI:10.1038/s41551-022-00920-3
PMID:35970930
Abstract

Optogenetics and calcium imaging can be combined to simultaneously stimulate and record neural activity in vivo. However, this usually requires two-photon microscopes, which are not portable nor affordable. Here we report the design and implementation of a miniaturized one-photon endoscope for performing simultaneous optogenetic stimulation and calcium imaging. By integrating digital micromirrors, the endoscope makes it possible to activate any neuron of choice within the field of view, and to apply arbitrary spatiotemporal patterns of photostimulation while imaging calcium activity. We used the endoscope to image striatal neurons from either the direct pathway or the indirect pathway in freely moving mice while activating any chosen neuron in the field of view. The endoscope also allows for the selection of neurons based on their relationship with specific animal behaviour, and to recreate the behaviour by mimicking the natural neural activity with photostimulation. The miniaturized endoscope may facilitate the study of how neural activity gives rise to behaviour in freely moving animals.

摘要

光遗传学和钙成像技术可以结合起来,在体内同时刺激和记录神经活动。然而,这通常需要双光子显微镜,这种显微镜既不便于携带,价格也昂贵。在此,我们报告了一种用于同时进行光遗传学刺激和钙成像的小型化单光子内窥镜的设计与实现。通过集成数字微镜,该内窥镜能够激活视野内任意选定的神经元,并在对钙活性进行成像的同时施加任意时空模式的光刺激。我们使用该内窥镜对自由活动小鼠中直接通路或间接通路的纹状体神经元进行成像,同时激活视野内任意选定的神经元。该内窥镜还能够根据神经元与特定动物行为的关系来选择神经元,并通过用光刺激模拟自然神经活动来重现行为。这种小型化内窥镜可能会促进对自由活动动物中神经活动如何产生行为的研究。

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