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Faculty Members


Molecular Neuropharmacology(Medical and Health Sciences)

Hashimoto HitoshiProfessor

It is generally accepted that psychiatric disorders are complex diseases that probably result from an interaction of genetic and environmental risk factors. However, little is known about the underlying molecular mechanisms. Therefore, scientific research on the brain and neuropsychological functions as well as the disorders is significantly important and is considered to continue to be a crucial research field of pharmacology.
We have been working on the identification and evaluation of new molecular targets for the development of drugs, by employing state-of-art molecular biology and animal models. In order to achieve this worthy aim, we will further introduce front-line methodological approaches and advance original pharmaceutical research on drug discovery.

Research theme

Development of high-speed and scalable whole-brain imaging technique

Whole-brain imaging techniques at resolutions sufficient to image all brain cells had been a challenge due to the trade-offs between speed and spatial resolution. To overcome the issue, we attempted to increase the imaging throughput and recently developed a high-speed serial-sectioning imaging system named FAST (block-FAce Serial microscopy Tomography) that employs spinning disk-based confocal microscopy and images a whole mouse brain in 2.4 h. FAST provides a versatile and robust method for whole-brain cell imaging with no limitations related to size that would contribute to a better understanding of the anatomical and functional brain networks in multiple animal models and in humans.

Identification and evaluation of novel molecular targets for drug discovery based on understanding of the brain

We believe that understanding the molecular mechanisms of the brain will lead to elucidation of pathophysiology and drug development for psychiatric and neurologic disorders. In our recent research using unbiased and hypothesis-free approaches, we revealed a small population of brain neurons control stress-induced anxiety responses. The findings are expected to unravel the pathogenesis of stress-related mental disorders and new treatment targets.

Representative achievements

M. Niu, A. Kasai, M. Tanuma, K. Seiriki, H. Igarashi, T. Kuwaki, K. Nagayasu, K. Miyaji, H. Ueno, W. Tanabe, K. Seo, R. Yokoyama, J. Ohkubo, Y. Ago, M. Hayashida, K. Inoue, M. Takada, S. Yamaguchi, T. Nakazawa, S. Kaneko, H. Okuno, A. Yamanaka, H. Hashimoto.
Claustrum mediates bidirectional and reversible control of stress-induced anxiety responses.
Science Advances. in press


Ichimura T, Kakizuka T, Horikawa K, Seiriki K, Kasai A, Hashimoto H, Fujita K, Watanabe TM, Nagai T.
Exploring rare cellular activity in more than one million cells by a transscale scope.
Scientific Reports. 2021; 11: 16539.

Kawaguchi C, Shintani N, Hayata-Takano A, Hatanaka M, Kuromi A, Nakamura R, Yamano Y, Shintani Y, Nagai K, Tsuchiya S, Sugimoto Y, Ichikawa A, Okuno Y, Urade Y, Hirai H, Nagata KY, Nakamura M, Narumiya S, Nakazawa T, Kasai A, Ago Y, Takuma K, Baba A, Hashimoto H.
Lipocalin-type prostaglandin D synthase regulates light-induced phase advance of the central circadian rhythm in mice.
Communications Biology. 2020; 3: 557.

Tanuma M, Kasai A, Bando K, Kotoku N, Harada K, Minoshima M, Higashino K, Kimishima A, Arai M, Ago Y, Seiriki K, Kikuchi K, Kawata S, Fujita K, Hashimoto H.
Direct visualization of an antidepressant analog using surface-enhanced Raman scattering in the brain.
JCI Insight. 2020; 5: e133348.

K. Matsumura, K. Seiriki, S. Okada, M. Nagase, S. Ayabe, I. Yamada, T. Furuse, H. Shibuya, Y. Yasuda, H. Yamamori, M. Fujimoto, K. Nagayasu, K. Yamamoto, K. Kitagawa, H. Miura, N. Gotoda-Nishimura, H. Igarashi, M. Hayashida, M. Baba, M. Kondo, S. Hasebe, K. Ueshima, A. Kasai, Y. Ago, A. Hayata-Takano, N. Shintani, T. Iguchi, M. Sato, S. Yamaguchi, M. Tamura, S. Wakana, A. Yoshiki, AM. Watabe, H. Okano, K. Takuma, R. Hashimoto, H. Hashimoto, T. Nakazawa.
Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes.
Nature Communications. 2020; 11: 859-859.

Seiriki K, Kasai A, Nakazawa T, Niu M, Naka Y, Tanuma M, Igarashi H, Yamaura K, Hayata-Takano A, Ago Y, Hashimoto H.
Whole-brain block-face serial microscopy tomography at subcellular resolution using FAST.
Nature Protocols. 2019; 14: 1509-1529.

Seiriki K, Kasai A, Hashimoto T, Schulze W, Niu M, Yamaguchi S, Nakazawa T, Inoue KI, Uezono S, Takada M, Naka Y, Igarashi H, Tanuma M, Waschek JA, Ago Y, Tanaka KF, Hayata-Takano A, Nagayasu K, Shintani N, Hashimoto R, Kunii Y, Hino M, Matsumoto J, Yabe H, Nagai T, Fujita K, Matsuda T, Takuma K, Baba A, Hashimoto H.
High-Speed and Scalable Whole-Brain Imaging in Rodents and Primates.
Neuron. 2017; 94: 1085-1100.

Nakazawa T, Hashimoto R, Sakoori K, Sugaya Y, Tanimura A, Hashimotodani Y, Ohi K, Yamamori H, Yasuda Y, Umeda-Yano S, Kiyama Y, Konno K, Inoue T, Yokoyama K, Inoue T, Numata S, Ohnuma T, Iwata N, Ozaki N, Hashimoto H, Watanabe M, Manabe T, Yamamoto T, Takeda M, Kano M.
Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders.
Nature Communications. 2016; 7: 10594.

Watanabe K, Palonpon AF, Smith NI, Chiu LD, Kasai A, Hashimoto H, Kawata S, Fujita K.
Structured line illumination Raman microscopy.
Nature Communications. 2015; 6: 10095.

Nakamachi T, Ohtaki H, Seki T, Yofu S, Kagami N, Hashimoto H, Shintani N, Baba A, Mark L, Lanekoff I, Kiss P, Farkas J, Reglodi D, Shioda S.
PACAP suppresses dry eye signs by stimulating tear secretion.
Nature Communications. 2016; 7: 12034.