Neural Circuit and Synaptic Mechanisms of Learning and Memory
Neuronal circuits made by synapses in the brain enable learning, memory, perception, emotion, and their impairment results in various mental disorders. We perform research that extensively utilize microscopic methods to observe cellular and molecular events deep within the brain, and which allow labeling of potentiated synapses and optical manipulation of synapses and circuits. We have shown that cerebral spine synapses undergo rapid enlargement during potentiation in the hippocampus, neocortex and basal ganglia. Such dynamic synaptic motilities are the sites of endogenous neuromodulation, therapeutic agents and addictive drugs. Moreover, the dynamic nature of synapses has allowed us to construct new optical and molecular probes for a better understanding of learning and cognition and their impairments.
Noguchi, J., Hayama, T., Watanabe, S., Ucar, H., Yagishita, S., Takahashi, N. & Kasai, H. (2016) State-dependent diffusion of actin-depolymerizing factor/cofilin underlies the enlargement and shrinkage of dendritic spines. Scientific Reports 6: 32897.
Hayashi-Takagi, A., Yagishita, S., Nakamura, M. Shirai, F., Wu, Y., Loshbaugh, A.L., Kuhlman, B., Hahn, K.M. and Kasai, H. (2015). Labelling and optical erasure of synaptic memory traces in the motor cortex. Nature 525:333-338.
Takahashi, N., Sawada, W., Noguchi, J., Watanabe, S., Ucar, H., Hayashi-Takagi, A., Yagishita, S., Ohno, M., Tokumaru, H. & Kasai, H. (2015). Two-photon fluorescence lifetime imaging of primed SNARE complexes in presynaptic terminals and beta cells.
Nature Comm. 6:8531.
Yagishita, S., Hayashi-Takagi, A., Ellis-Davies, G.C.R., Urakubo, H., Ishii, S. & Kasai, H. (2014). A critical time window for dopamine action on the structural plasticity of dendritic spines. Science 345:1616-1620.
Hayama, T., Noguchi, J., Watanabe, S., Ellis-Davies, G.C.R., Hayashi, A., Takahashi, N., Matsuzaki, M. & Kasai, H. (2013). GABA promotes the competitive selection of dendritic spines by controlling local Ca2+ signaling. Nature Neurosci 16:1409-1416.
Tanaka, J., Horiike, Y., Matsuzaki, M., Miyazaki, T., Ellis-Davies, G.C.R. & Kasai, H. (2008). Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Science 319:1683-1687.
Matsuzaki, M., Honkura, N., Ellis-Davies, G.C.R. & Kasai, H. (2004). Structural basis of long-term potentiation in single dendritic spines. Nature 429:761-766.
I graduated from the University of Tokyo School of Medicine and became a Humboldt fellow in the Max-Planck Institute, Germany. After coming back to Japan, I was an Assistant and then Associate Professor of the Physiology Department of the University of Tokyo, and promoted to Professor of the National Institute of Physiological Sciences, Okazaki. Currently, I have been developing optical methods (two-photon uncaging of caged-glutamate), and revealed that synaptic morphology shows a tight correlation with connectivity, and synapses rapidly enlarge when learning stimuli are given to enhance connectivity. I then moved to the Center for Disease and Integrative Medicine in the University of Tokyo, where I have been pursuing optical and molecular investigations of learning and memory in the brain and its related psychiatric disorders.