Neurocomputation of schizophrenia pathophysiology based on the two-photon synaptic imaging in vivo

2017 Fiscal Year Final Research Report

• Project/Area Number: 26293260
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Gunma University (2016-2017); The University of Tokyo (2014-2015)
• Principal Investigator: Hayashi-Takagi Akiko (高木朗子) 群馬大学, 生体調節研究所, 教授 (60415271)
• Co-Investigator(Kenkyū-buntansha): 田中 昌司 上智大学, 理工学部, 教授 (30188304)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 統合失調症 / シナプス / 2光子イメージング / シナプス後電流

Outline of Final Research Achievements

DISC1 is one of schizophrenia-related gene. We performed the longitudinal in vivo imaging analysis of the brain of DISC1 knockdown model, and we found this model exhibited decrease in the dendritic spine and the significant increase in the huge spines. The existent of the huge spines in this model mice is interesting because another schizophrenia model mice, Calcineurin knockout mice also exhibited this phenomenon. Given that there is the strong correlation between spine head size and its synaptic efficacy, the huge spine can generate larger synaptic current. Furthermore, multiple synaptic inputs are integrated in dendrite, resulting in the generation of NMDA spike, and simultaneous inputs within dendritic segment induces supralinear effect for the generation of NMDA spike. We are now demonstrating that the larger current through the huge spine would significantly change dendritic integration, resulting in disorganized firing.

Free Research Field

神経科学