Virtual reality-based real-time imaging reveals abnormal cortical dynamics during behavioral transitions in a mouse model of autism

Nobuhiro Nakai; Masaaki Sato; Okito Yamashita; Yukiko Sekine; Xiaochen Fu; Junichi Nakai; Andrew Zalesky; Toru Takumi

doi:10.1016/j.celrep.2023.112258

Virtual reality-based real-time imaging reveals abnormal cortical dynamics during behavioral transitions in a mouse model of autism

Cell Rep. 2023 Apr 25;42(4):112258. doi: 10.1016/j.celrep.2023.112258. Epub 2023 Mar 28.

Authors

Nobuhiro Nakai¹, Masaaki Sato², Okito Yamashita³, Yukiko Sekine⁴, Xiaochen Fu⁴, Junichi Nakai⁵, Andrew Zalesky⁶, Toru Takumi⁷

Affiliations

¹ RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan; Department of Physiology and Cell Biology, Kobe University School of Medicine, Chuo, Kobe 650-0017, Japan.
² RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan; Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, Kita, Sapporo 060-8638, Japan. Electronic address: msato@pop.med.hokudai.ac.jp.
³ RIKEN Center for Advanced Intelligence Project, Chuo, Tokyo 103-0027, Japan; Department of Computational Brain Imaging, ATR Neural Information Analysis Laboratories, Seika, Kyoto 619-0288, Japan.
⁴ RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
⁵ Division of Oral Physiology, Department of Disease Management Dentistry, Tohoku University Graduate School of Dentistry, Aoba, Sendai 980-8575, Japan.
⁶ Melbourne Neuropsychiatry Centre and Department of Biomedical Engineering, The University of Melbourne, Melbourne, VIC 3010, Australia.
⁷ RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan; Department of Physiology and Cell Biology, Kobe University School of Medicine, Chuo, Kobe 650-0017, Japan; RIKEN Center for Biosystems Dynamics Research, Chuo, Kobe 650-0047, Japan. Electronic address: takumit@med.kobe-u.ac.jp.

PMID: 36990094
DOI: 10.1016/j.celrep.2023.112258

Abstract

Functional connectivity (FC) can provide insight into cortical circuit dysfunction in neuropsychiatric disorders. However, dynamic changes in FC related to locomotion with sensory feedback remain to be elucidated. To investigate FC dynamics in locomoting mice, we develop mesoscopic Ca²⁺ imaging with a virtual reality (VR) environment. We find rapid reorganization of cortical FC in response to changing behavioral states. By using machine learning classification, behavioral states are accurately decoded. We then use our VR-based imaging system to study cortical FC in a mouse model of autism and find that locomotion states are associated with altered FC dynamics. Furthermore, we identify FC patterns involving the motor area as the most distinguishing features of the autism mice from wild-type mice during behavioral transitions, which might correlate with motor clumsiness in individuals with autism. Our VR-based real-time imaging system provides crucial information to understand FC dynamics linked to behavioral abnormality of neuropsychiatric disorders.

Keywords: ASD; CP: Neuroscience; VR; cortex; functional connectivity; locomotion behavior; machine learning; mesoscopic Ca(2+) imaging; mouse model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autism Spectrum Disorder*
Autistic Disorder* / diagnostic imaging
Disease Models, Animal
Locomotion
Machine Learning
Magnetic Resonance Imaging / methods
Mice
Social Behavior
Virtual Reality*