Unraveling the physiological function of developing cerebellar activity for thalamo-cortical circuit formation

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20705
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0704:Neuroscience, brain sciences, and related fields
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Kamijo Satoshi 国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 精神薬理研究部, リサーチフェロー (20910491)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 小脳 / 自閉症スペクトラム障害 / プルキンエ細胞 / 脳の性差

Outline of Final Research Achievements

Focusing on the "developmental cerebellar dysfunction hypothesis" that abnormal cerebellar activity during the developmental period is the primary cause of autism spectrum disorder (ASD), we showed that suppressing Purkinje neurons’ activity from postnatal day 11 to 15 caused male-specific social deficits. Other ASD-like phenotypes such as repetitive behaviors were not observed in both males and females, suggesting that each phenotype has a unique critical period and that the susceptibility to abnormal cerebellar activity differs by sex. It is reported that ASD patients have sensory abnormalities at high rates. To investigate the relationship between the cerebellum and the sensory abnormalities, we set up widefield calcium imaging system to measure the cortical response to various sensory stimuli and adopted a novel method to analyze the data in a highly interpretable manner.

Free Research Field

自閉症スペクトラム障害

Academic Significance and Societal Importance of the Research Achievements

発達期の小脳活動の異常が成体の行動に影響を与えることは、ASDの発達期小脳機能異常仮説をより強固にするのみならず、ASDで見られる諸症状のうち、何が可逆か（治療可能性）、治療をいつ開始すべきか（介入時期の決定）といった疑問へのヒントを与えている。また、オスのみで表現型が観察されたことは、ASD患者が男児に多い事実と符合し、小脳活動の異常に対する感受性の違いによってASD患者の性比の偏りを説明できる可能性を示唆している。