Principal Investigator
Technology
Project Professor
Neural Circuit and Synaptic Mechanisms of Memory and Cognitive Function
Research
Neuronal circuits formed by synapses in the brain enable learning, memory, perception, and emotion, and their impairment results in various mental disorders. We extensively utilize two-photon microscopy to observe cellular and molecular events deep within the brain, enabling optical recording, manipulation and electrophysiology of synapses and neuronal circuits. By developing two-photon uncaging, we demonstrated rapid enlargement of dendritic spines during potentiation in the hippocampus, neocortex, and basal ganglia, underpinning long-term potentiation (LTP), dopamine modulation of single dendritic spines, intrinsic synaptic dynamics and rapid mechanical actions of spine enlargement on presynaptic terminal (mechanical synaptic transmission) preceding LTP. We also invented Synaptic Chemogenetics (SYNCit) to manipulate spine synapses in broad cortical areas, revealing dendritic spine control over sleep homeostasis, cortical wakefulness, and rapid cognitive functions. Our advancements in molecular labeling of active spines together with SYNCit approaches, visualizing the cellular basis of memory and cognition, new treatments for mental disorders, and novel concepts for artificial intelligence.
Publications
Sawada,T., Iino, Y., Yoshida, K., Okazaki, H., Nomura, S., Shimizu, C., Arima, T., Juichi, T., Zhou, S., Kurabayashi, N., Sakurai, T., Yagishita, S., Yanagisawa, M., Toyoizumi, T., Kasai, H.*, Shi, S.* (2024) Prefrontal synaptic regulation of homeostatic sleep pressure revealed through synaptic chemogenetics. Science, 385, 1459-1465.
Ucar, H., Morimoto, Y., Watanabe, S., Noguchi, J., Iino, Y., Yagishita, S., Takahashi, N. and Kasai, H.* Mechanical actions of dendritic-spine enlargement on presynaptic exocytosis. Nature 600; 686-689, 2021.
Iino, Y., Sawada, T., Yamaguchi, Tajiri, M., K., Ishii, S., Kasai, H.* and Yagishita, S.* Dopamine D2 receptors in discrimination learning and spine enlargement. Nature, 579; 555-560, 2020.
Hayashi-Takagi, A., Yagishita, S., Nakamura, M. Shirai, F., Wu, Y., Loshbaugh, A.L., Kuhlman, B., Hahn, K.M. and Kasai, H.* Labelling and optical erasure of synaptic memory traces in the motor cortex. Nature 525; 333-338, 2015.
Yagishita, S., Hayashi-Takagi, A., Ellis-Davies, G.C.R., Urakubo, H., Ishii, S. and Kasai, H.* A critical time window for dopamine action on the structural plasticity of dendritic spines. Science 345; 1616-1620, 2014.
Tanaka, J., Horiike, Y., Matsuzaki, M., Miyazaki, T., Ellis-Davies, G.C.R. and Kasai, H.* Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Science 319; 1683-1687, 2008.
Matsuzaki, M., Honkura, N., Ellis-Davies, G.C.R. and Kasai, H.* Structural basis of long-term potentiation in single dendritic spines. Nature 429; 761-766, 2004.
Biography
Haruo Kasai graduated from the University of Tokyo School of Medicine, training in Masao Ito's laboratory, and became a Humboldt Fellow at the Max-Planck Institute, Germany, under Erwin Neher. Upon returning to Japan, he served as Associate Professor of Physiology at the University of Tokyo and later as Professor at the National Institute of Physiological Sciences, pioneering two-photon uncaging of caged glutamate and discovered enlargement of dendritic spine. Returning to the Medical School of the University of Tokyo as Professor and becoming a PI at IRCN, he developed various new methods and discovered fast mechanical actions of spine enlargement on synaptic transmission and its roles in cognitive function.
