| Budget Amount *help |
¥176,800,000 (Direct Cost: ¥136,000,000、Indirect Cost: ¥40,800,000)
Fiscal Year 2022: ¥32,760,000 (Direct Cost: ¥25,200,000、Indirect Cost: ¥7,560,000)
Fiscal Year 2021: ¥37,570,000 (Direct Cost: ¥28,900,000、Indirect Cost: ¥8,670,000)
Fiscal Year 2020: ¥32,240,000 (Direct Cost: ¥24,800,000、Indirect Cost: ¥7,440,000)
Fiscal Year 2019: ¥31,460,000 (Direct Cost: ¥24,200,000、Indirect Cost: ¥7,260,000)
Fiscal Year 2018: ¥42,770,000 (Direct Cost: ¥32,900,000、Indirect Cost: ¥9,870,000)
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| Outline of Final Research Achievements |
In light of human genetics, there is little doubt regarding the involvement of synaptopathy in psychiatric disorders. However, trans-scale causality;from the synapse to behaviour is lacking. To address this question, we examined the multiscale effects of synaptic inputs of SETD1A and DISC1, which are validated animal models of schizophrenia. Both models exhibited an overrepresentation of extra-large (XL) synapses, which evoked supralinear synaptic integration, resulting in increased neuronal firing. The probability of XL spines correlated negatively with working memory, and the optical prevention of XL spine generation restored working memory impairment. Furthermore, XL synapses were significantly more abundant in the postmortem brains of schizophrenia patients than in those of matched controls. Our results suggest that certain domains of psychiatric symptoms are caused by hyper-connection via heavily-weighted synapses.
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