Developing a method for differential genetic manipulations on two types of neurons within a local neural circuit of the central circadian clock

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19421
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: Kanazawa University
• Principal Investigator: MIEDA Michihiro 金沢大学, 医学系, 教授 (20296552)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: サーカディアンリズム / 体内時計 / 視交叉上核 / 神経ネットワーク / 遺伝子操作マウス / アデノ随伴ウイルスベクター / 光遺伝学 / カルシウムセンサー

Outline of Final Research Achievements

Using the neural network of the central circadian clock of the suprachiasmatic nucleus (SCN) as a model, we aimed to construct a strategy for analyzing intercellular communications between different two types of neurons within a complex local circuit, by differential genetic and optogenetic manipulations on those different neuronal types. Its specific purposes include recording responses of one neuron type to the stimulation of another neuron type, recording activities of two types of neurons simultaneously, and uncovering upstream/downstream relationships between two types of neurons. To do this, we generated novel genetically-modified mouse lines and recombinant adeno-associated viral vectors. We also set up a system to record the neuronal activity of a particular type of neurons in vivo. Thus, we have successfully constructed such a strategy.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

中枢概日時計・視交叉上核神経ネットワークは、多種・多数の神経細胞間のコミュニケーションを介し、強固で安定な概日振動を発振する。しかしながら、視交叉上核の神経回路レベルでの動作原理に関する知見は驚くほど少ない。本研究は中枢概日時計神経ネットワークの動作原理解明において、これまでに無い斬新なアプローチを採るもので、学術的意義が大きい。加えて、神経科学・神経生理学全般に対し、複雑な局所神経回路網の機能を解析する上での、新たな方法論を提供する。また、概日時計の変調や他の局所神経回路の異常に起因する健康障害・疾患の病態生理の理解、さらにはその対処法の開発に繋がれば、社会的意義も大きい。