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

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 us-ing machine learning classification, behavioral states are accurately decoded. We then use our VR-based im-aging 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 distin-guishing 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.

Automated summary

Functional connectivity (FC) in cortical circuit dysfunction can be revealed through mesoscopic Ca2+ imaging with a virtual reality environment. Rapid reorganization of cortical FC in response to changing behavioral states is observed, and machine learning classification accurately decodes behavioral states. The VR-based imaging system is used to study FC dynamics in a mouse model of autism, identifying FC patterns involving the motor area as distinguishing features during behavioral transitions and potentially correlating with motor clumsiness in individuals with autism. This VR-based system provides crucial information to understand FC dynamics in neuropsychiatric disorders.