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Social circuits and their dysfunction in autism spectrum disorder

Sato, Masaaki Nakai, Nobuhiro Fujima, Shuhei Choe, Y. Katrina Takumi, Tooru 神戸大学

2023.08.24

概要

Social behaviors, how individuals act cooperatively and competitively with conspecifics, are widely seen across species. Rodents display various social behaviors, and many different behavioral paradigms have been used for investigating their neural circuit bases. Social behavior is highly vulnerable to brain network dysfunction caused by neurological and neuropsychiatric conditions such as autism spectrum disorders (ASDs). Studying mouse models of ASD provides a promising avenue toward elucidating mechanisms of abnormal social behavior and potential therapeutic targets for treatment. In this review, we outline recent progress and key findings on neural circuit mechanisms underlying social behavior, with particular emphasis on rodent studies that monitor and manipulate the activity of specific circuits using modern systems neuroscience approaches. Social behavior is mediated by a distributed brain-wide network among major cortical (e.g., medial prefrontal cortex (mPFC), anterior cingulate cortex, and insular cortex (IC)) and subcortical (e.g., nucleus accumbens, basolateral amygdala (BLA), and ventral tegmental area) structures, influenced by multiple neuromodulatory systems (e.g., oxytocin, dopamine, and serotonin). We particularly draw special attention to IC as a unique cortical area that mediates multisensory integration, encoding of ongoing social interaction, social decision-making, emotion, and empathy. Additionally, a synthesis of studies investigating ASD mouse models demonstrates that dysfunctions in mPFC-BLA circuitry and neuromodulation are prominent. Pharmacological rescues by local or systemic (e.g., oral) administration of various drugs have provided valuable clues for developing new therapeutic agents for ASD. Future efforts and technological advances will push forward the next frontiers in this field, such as the elucidation of brain-wide network activity and inter-brain neural dynamics during real and virtual social interactions, and the establishment of circuit-based therapy for disorders affecting social functions.

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ACKNOWLEDGEMENTS

We thank Yu Ohmura for his valuable comments on this manuscript.

AUTHOR CONTRIBUTIONS

MS, NN, SF, KYC, and TT wrote and edited the manuscript.

FUNDING

The authors receive financial support from: The KAKENHI from JSPS (20H03550 and

23H02668) and Taiju Life Social Welfare Foundation to MS; The KAKENHI from JSPS

(23K14673 and 23H04138) to NN; The KAKENHI from JSPS (16H06316, 16H06463,

21H00202, 21H04813, and 23H04233), Japan Agency for Medical Research and

Development (JP21wm0425011), Japan Science and Technology Agency (JPMJMS2299

and JPMJMS229B), Intramural Research Grant (30-9) for Neurological and Psychiatric

Disorders of NCNP, The Takeda Science Foundation, Research Foundation for OptoScience and Technology, Taiju Life Social Welfare Foundation, The Naito Foundation,

The Tokumori Yasumoto Memorial Trust for Researches on Tuberous Sclerosis Complex

and Related Rare Neurological Diseases to TT, and the Canada Research Chairs Program

to KYC. Open access funding provided by Kobe University.

COMPETING INTERESTS

The authors declare no competing interests.

ADDITIONAL INFORMATION

Correspondence and requests for materials should be addressed to Toru Takumi.

Reprints and permission information is available at http://www.nature.com/

reprints

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in published maps and institutional affiliations.

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