L Shigeyoshi Itohara, Behavioral Genetics | RIKEN Center for Brain Science (RIKEN CBS)

We aim to elucidate circuit and molecular mechanisms underlying attention and related behaviors.

Shigeyoshi ItoharaShigeyoshi Itohara

Shigeyoshi Itohara, D.V.M., Ph.D.

Team Leader, Behavioral Genetics
shigeyoshi.itohara [at] riken.jp

Research Overview

Animal behavior relies on the integration of complex external and internal information in the brain. Highly organized molecular and cellular networks underlie this integration. These networks are defined largely by genetic factors and partly by environmental factors, and their subtle differences among individuals underlie differences in personality and temperament. Abnormalities in these networks caused by various factors, including injury, infection, social and physical stress, and genetics, might result in cognitive deficits and various mental disorders. We are interested in learning how highly organized networks are established in the mammalian central nervous system (CNS); how the networks are modulated by environmental factors; and the mechanisms that underlie the integration and/or differentiation of distinct information inputs. Mutant mice generated by reverse genetics are indispensable for examining these issues because they allow for the study of an unambiguous cause-effect relationship at any phenotype level. In our laboratory, we have developed and refined genetic engineering methods to produce mice with the required novel genetic traits. Our current aims include the elucidation of molecular and cellular mechanisms underlying attention and impulsivity. Sleep abnormalities are associated with various mental disorders. Thus, we also aim to elucidate neuronal circuits regulating sleep.

Main Research Field

Related Research Fields


Selected Publications

  1. Yasuda, K., Hayashi, Y., Yoshida, T., Kashiwagi, M., Nakagawa, N., Michikawa, T., Tanaka, M., Ando, R., Huang, A., Hosoya, T., McHugh, T.J., Kuwahara, M., and Itohara S.:
    "Schizophrenia-like phenotypes in mice with NMDA receptor ablation in intralaminar thalamic nucleus cells and gene therapy-based reversal in adults."
    Transl. Psychiatry, 7 (2): e1047 (2017).
  2. Zhang, Q., Goto, H., Akiyoshi-Nishimura, S., Prosselkov, P., Sano, C., Matsukawa, H., Yaguchi, K., Nakashiba, T., and Itohara, S.:
    "Diversification of behavior and postsynaptic properties by netrin-G presynaptic adhesion family proteins."
    Mol. Brain 9(1): 6 (2016).
  3. Hayashi, Y., Kashiwagi, M., Yasuda, K., Ando, R., Kanuka, M., Sakai, K., and Itohara, S.:
    "Cells of a common developmental origin regulate REM/non-REM sleep and wakefulness in mice."
    Science 350(6263): 957-961 (2015).
  4. Iwata, R., Matsukawa, H., Yasuda, K., Mizuno, H., Itohara, S., and Iwasato, T.:
    "Developmental RacGAP α2-chimaerin signaling is a determinant of the morphological features of dendritic spines in adulthood."
    J. Neurosci., 35(40): 13728-13744 (2015).
  5. Matsukawa, H., Akiyoshi-Nishimura, S,. Zhang, Q., Luján, R., Yamaguchim,K., Goto, H., Yaguchi, K., Hashikawa, T., Sano, C., Shigemoto R., Nakashiba, T., and Itohara S.:
    "Netrin-G/NGL complexes encode functional synaptic diversification."
    J. Neurosci., 34(47): 15779-15792 (2014).
  6. Iwata, R., Ohi, K., Kobayashi, Y., Masuda, A., Iwama, M., Yasuda, Y., Yamamori, H., Tanaka, M., Hashimoto, R., Itohara, S., and Iwasato, T.:
    "RacGAP α2-chimaerin function in development adjusts cognitive ability in adulthood."
    Cell Rep., 8(5): 1257-1264 (2014).
  7. Mizuno, H., Luo, W., Tarusawa, E., Saito, Y.M., Sato, T., Yoshimura, Y., Itohara, S., and Iwasato, T.:
    "NMDAR-regulated dynamics of layer 4 neuronal dendrites during thalamocortical reorganization in neonates."
    Neuron 82(2): 365-379 (2014).
  8. Kobayashi, Y., Sano, Y., Vannoni, E., Goto, H., Suzuki, H., Oba, A., Kawasaki, H., Kanba, S., Lipp, H.P., Murphy, N.P., Wolfer, D.P., and Itohara S.:
    "Genetic dissection of medial habenula-interpeduncular nucleus pathway function in mice."
    Front. Behav. Neurosci.. 7, 17 (2013).
  9. Nishimura-Akiyoshi, S., Niimi, K., Nakashiba, T., and Itohara, S.:
    "Axonal netrin-Gs transneuronally determine lamina-specific subdendritic segments."
    Proc. Natl. Acad. Sci. USA 104(37): 14801-14806 (2007).
  10. Iwasato, T., Katoh, H., Nishimaru, H., Ishikawa, Y., Inoue, H., Saito, Y.M., Ando, R., Iwama, M., Takahashi, R., Negishi, M., and Itohara, S.:
    "Rac-GAP α-Chimerin Regulates Motor-Circuit Formation as a Key Mediator of EphrinB3/EphA4 Forward Signaling."
    Cell 130(4): 742-753 (2007).

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