Large-Scale 3D Two-Photon Imaging of Molecularly Identified CA1 Interneuron Dynamics in Behaving Mice

• Published in: Neuron (Cambridge, Mass.) Vol. 108; no. 5; pp. 968 - 983.e9
• Main Authors: Geiller, Tristan, Vancura, Bert, Terada, Satoshi, Troullinou, Eirini, Chavlis, Spyridon, Tsagkatakis, Grigorios, Tsakalides, Panagiotis, Ócsai, Katalin, Poirazi, Panayiota, Rózsa, Balázs J., Losonczy, Attila
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.12.2020; Elsevier Limited
• Subjects: Animals; axo-axonic; Behavior; CA1 Region, Hippocampal - chemistry; CA1 Region, Hippocampal - cytology; CA1 Region, Hippocampal - diagnostic imaging; calcium; Calcium - analysis; Calcium - metabolism; Calcium imaging; CCK; context; Female; Hippocampus; imaging; Imaging, Three-Dimensional - methods; Immunohistochemistry; interneuron; Interneurons; Interneurons - chemistry; Interneurons - ultrastructure; Male; Memory; Mice; Mice, Transgenic; Microscopy; Microscopy, Confocal - methods; Microscopy, Fluorescence, Multiphoton - methods; Navigation behavior; remapping; reward; sharp-wave ripple; Velocity; γ-Aminobutyric acid; reward; sharp-wave ripple; axo-axonic; calcium; hippocampus; remapping; context; interneuron; CCK; imaging
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2020.09.013

Cortical computations are critically reliant on their local circuit, GABAergic cells. In the hippocampus, a large body of work has identified an unprecedented diversity of GABAergic interneurons with pronounced anatomical, molecular, and physiological differences. Yet little is known about the functional properties and activity dynamics of the major hippocampal interneuron classes in behaving animals. Here we use fast, targeted, three-dimensional (3D) two-photon calcium imaging coupled with immunohistochemistry-based molecular identification to retrospectively map in vivo activity onto multiple classes of interneurons in the mouse hippocampal area CA1 during head-fixed exploration and goal-directed learning. We find examples of preferential subtype recruitment with quantitative differences in response properties and feature selectivity during key behavioral tasks and states. These results provide new insights into the collective organization of local inhibitory circuits supporting navigational and mnemonic functions of the hippocampus. •A subset of CA1 interneurons exhibit spatially tuned activity•Axo-axonic and bistratified cells show bimodal recruitment during sharp-wave ripples•SOM+ cells are preferentially recruited during goal-oriented spatial learning•Disinhibition from VIP+ cells is preferentially mediated through SOM+ cells Geiller et al. use 3D AOD-based two-photon functional imaging and post hoc immunohistochemistry in mouse hippocampal region CA1 to simultaneously image and characterize the dynamics of hundreds of molecularly defined interneurons in vivo during spatial navigation, quiet wakefulness, and goal-oriented spatial learning.