Journal Article

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

Ding, Lingjun, Chen, Hongbiao, Zouridis, Ioannis S, Naumann, Robert, Preston-Ferrer, Patricia, Burgalossi, Andrea, Balsamo, Giuseppe, Blanco-Hernandez, Eduardo

2022

Overview

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.

• Publisher: eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Action Potentials - physiology / Animals / CA1 Region, Hippocampal - chemistry / CA1 Region, Hippocampal - physiology / Calbindin / Calbindins - genetics / Channelrhodopsins - metabolism / Classification / Gene expression / Genetics / Hippocampus / Hippocampus - metabolism / Information processing / juxtacellular recordings / Labeling / Light / Male / Marking and tracking techniques / Mice / Mice, Inbred C57BL / Morphology / Movement - physiology / Neural circuitry / Neural networks / Neurons / Neurons - physiology / Neuroscience / Optics / Optogenetics - methods / optotagging / place cells / Pyramidal cells / Pyramidal Cells - chemistry / Pyramidal Cells - physiology / pyramidal neurons / Structure-function relationships / Tools and Resources