Study of cerebral synapses and circuits using two-photon microscopy and novel optoprobes

2018 Fiscal Year Final Research Report

• Project/Area Number: 26221001
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Neurophysiology / General neuroscience
• Research Institution: The University of Tokyo
• Principal Investigator: Kasai Haruo 東京大学, 大学院医学系研究科(医学部), 教授 (60224375)
• Co-Investigator(Kenkyū-buntansha): 林 朗子 (高木朗子) 東京大学, 医学(系)研究科(研究院), 講師 (60415271)
• Research Collaborator: TAKAHASHI Noriko ; NOGUCHI Jun ; YAGISHITA Sho
• Project Period (FY): 2014-05-30 – 2019-03-31
• Keywords: シナプス / 学習・記憶 / ドーパミン / 大脳皮質 / 大脳基底核 / グルタミン酸

Outline of Final Research Achievements

We have developed the synaptic probe (AS-probe) that can label and erase the labeled dendritic spines by blue laser irradiation. Using AS-probe, we have operationally shown the involvement of spines in motor learning in the motor cortex (Nature 2015) and anti-depressant effects of spine generations in the prefrontal cortex by s-ketamine (Science 2019). We are extending our technique to presynaptic boutons (in preparation). We also studied the cellular mechanisms of the reward classical conditioning, and found that the spine enlargement of D1 neurons can explain the reward timing found in earlier works (Science 2014). We have also clarified that discrimination learning involves spine enlargement of D2 neurons, and is impaired in psychotic symptoms which can be ameliorated by D2 antagonist (an antipsychotic drug), pointing to a new understanding of D2 receptors (in preparations).

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

心を育む脳の働きは神経回路の電気化学的活動で起きると信じられている。しかし、学習するときには、これに加えて神経を繋ぐシナプスが運動することを我々は見出し、これが運動学習、うつ症状など個体レベルで使われていることを証明した(Nature 2015, Science 2019)。また、条件付け学習の際には、脳内報酬信号であるドーパミンは適切なタイミングで神経から放出されれば記憶を強く促す作用があることを明らかにした(Science 2014)。この個性的に運動する脳の描像は我々の個性や病気を理解する新しい鍵となるであろう。