Transformation of the relationship between synaptic supramolecular assemblies and synaptic function in mental disorder

2016 Fiscal Year Final Research Report

• Project Area: Unraveling micro-endophenotypes of psychiatric disorders at the molecular, cellular and circuit levels.
• Project/Area Number: 24116004
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: HIROSE Kenzo 東京大学, 大学院医学系研究科(医学部), 教授 (00292730)
• Co-Investigator(Renkei-kenkyūsha): ASANUMA Daisuke 東京大学, 大学院医学系研究科, 助教 (10611204) ; NAMIKI Shigeyuki 東京大学, 大学院医学系研究科, 助教 (90452193)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Keywords: 精神疾患 / シナプス / 超解像イメージング / 超分子構造

Outline of Final Research Achievements

We developed fluorescent probes for glutamate and acidic environment, and fluorescence labeling method for superresolution imaging for analyzing synaptic properties in psychiatric disease model animals. By using superresolution microscopy, we clarified transformation in size and number of nanoclusters formed by glutamate receptors in the hippocampus of Schnurri-2 knockout mice and dopaminergic receptors in striatum nucleus accumbens of DISC1 knockout mice, respectively. Further we revealed that the aberration of D2R nanocluster in DISC1 knockout mouse was ameliorated to the level of wild type by administration of antipsychotic drug clozapine. Our studies show that changes of nano-scale molecular assemblies could be a microendophenotype of psychiatric diseases.

Free Research Field

神経生物学・薬理学