Juxtacellular opto-tagging of hippocampal CA1 neurons in freely moving mice

eLife

Robert Naumann¹  Andrea Burgalossi²  Eduardo Blanco-Hernandez²  Patricia Preston-Ferrer²  Lingjun Ding³  Ioannis S Zouridis³  Hongbiao Chen³  Giuseppe Balsamo³ 

[1] Chinese Academy of Sciences, Key Laboratory of Brain Connectome and Manipulation, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Nanshan, China;Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China;Institute of Neurobiology, Eberhard Karls University of Tübingen, Tübingen, Germany;Werner-Reichardt Centre for Integrative Neuroscience, Tübingen, Germany;Institute of Neurobiology, Eberhard Karls University of Tübingen, Tübingen, Germany;Werner-Reichardt Centre for Integrative Neuroscience, Tübingen, Germany;Graduate Training Centre of Neuroscience – International Max-Planck Research School (IMPRS), Tübingen, Germany;

关键词: hippocampus;    place cells;    pyramidal neurons;    juxtacellular recordings;    optotagging;    Mouse;   

DOI  :  10.7554/eLife.71720

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Neural circuits are made of a vast diversity of neuronal cell types. While immense progress has been made in classifying neurons based on morphological, molecular, and functional properties, understanding how this heterogeneity contributes to brain function during natural behavior has remained largely unresolved. In the present study, we combined the juxtacellular recording and labeling technique with optogenetics in freely moving mice. This allowed us to selectively target molecularly defined cell classes for in vivo single-cell recordings and morphological analysis. We validated this strategy in the CA1 region of the mouse hippocampus by restricting Channelrhodopsin expression to Calbindin-positive neurons. Directly versus indirectly light-activated neurons could be readily distinguished based on the latencies of light-evoked spikes, with juxtacellular labeling and post hoc histological analysis providing ‘ground-truth’ validation. Using these opto-juxtacellular procedures in freely moving mice, we found that Calbindin-positive CA1 pyramidal cells were weakly spatially modulated and conveyed less spatial information than Calbindin-negative neurons – pointing to pyramidal cell identity as a key determinant for neuronal recruitment into the hippocampal spatial map. Thus, our method complements current in vivo techniques by enabling optogenetic-assisted structure–function analysis of single neurons recorded during natural, unrestrained behavior.

【 授权许可】

CC BY