Tomoyuki Takahashi

Research Career

After training as a medical doctor, Dr. Tomoyuki Takahashi received his Ph. D. degree in Pharmacology from Tokyo Medical & Dental University in 1975 for his pioneering works on substance P as a neurotransmitter in cat spinal cord. In post-doctoral training, he worked with Dr. Ricardo Miledi at the Biophysics Department, University College London, being supervised by Sir Bernard Katz. After returning to Japan, he collaborated with Dr. Shosaku Numa's group at Kyoto University as a lecturer in Dr. Motoy Kuno's laboratory, and contributed to the establishment of the new field, Molecular Neuroscience. During the collaboration, he made friendships with Drs. Bert Sakmann, Erwin Neher and their colleagues, and this led him to develop patch-clamp method in brain slice preparations (Edwards et al. 1989). This method, called "slice-patch-clamp method", has widely been used among neuroscientists. Using this method, Dr. Takahashi and his colleagues have provided fundamental information on brain synaptic functions, such as identification of voltage-gated calcium channel subtypes mediating transmitter release (Takahashi & Momiyama, 1993). After he moved to the University of Tokyo as a professor, he collaborated with Dr. Ian Forsythe to develop a preparation in which one can make patch-clamp recordings from presynaptic and postsynaptic structures simultaneously (Takahashi et al. 1996). This preparation, the calyx of Held synapse in rodents, is now recognized as a gold model of mammalian central synapse, after frog neuromuscular junction and squid giant synapse. Using the calyx of Held synapse, Dr. Takahashi's group unveiled presynaptic mechanisms regulating transmitter release which had never been proved directly. As a leading scientist, Dr. Takahashi named on the editorial board of international journals, such as Science and The Journal of Physiology. After his retirement from the University of Tokyo in 2007, his scientific curiosity led him to continue working in Kyoto (Doshisha University) and thereafter in Okinawa (OIST) from 2015.

Selected Publications

Nakamura Y, Harada H, Kamasawa N, Matsui K, Rothman JS, Shigemoto R, Silver RA, DiGregorio DA, Takahashi T. (2015) Nanoscale distribution of presynaptic Ca²⁺channels and its impact on vesicular release during development.
Neuron 85, 145-158.

Takahashi T. (2015). Strength and precision of neurotransmission at mammalian presynaptic terminals.　Proc Japan Acad, Ser B 91, 305-320.

Testuya Hori and Tomoyuki Takahashi (2012).Kinetics of Synaptic Vesicle Refilling with Neurotransmitter Glutamate. Neuron 76, 511-517.

Kohgaku Eguchi, Setsuko Nakanishi, Hiroshi Takagi, Zacharie Taoufiq and Tomoyuki Takahashi (2012) Maturation of a PKG-Dependent Retrograde Mechanism for Exo-Endocytic Coupling of Synaptic Vesicles. Neuron 74, 517-529.

Yamashita T., Eguchi K., Saitoh N., von Gersdorff H. & Takahashi T. (2010). Developmental shift to a mechanism of synaptic vesicle endocytosis requiring nanodomain Ca²⁺. Nat. Neurosci. 13, 838-844.

Yamashita T., Hige T. & Takahashi T. (2005). Vesicle endocytosis requires dynamin-dependent GTP hydrolysis at a fast CNS synapse. Science 307, 124-127.

 Ishikawa T.*, Sahara Y.* & Takahashi T.(2002). A single packet of transmitter does not saturate postsynaptic glutamate receptors. Neuron 34, 613-621.

 Tsujimoto T.*, Jeromin A.*, Saitoh N., Roder JC. & Takahashi T. (2002). Neuronal calcium sensor 1 and activity-dependent facilitation of P/Q-type calcium currents at presynaptic nerve terminals. Science 295, 2276-2279.

 Takahashi T., Hori T., Kajikawa Y. & Tsujimoto T. (2000). The role of GTP-binding protein activity in fast central synaptic transmission. Science 289, 460-463.

Forsythe I.D., Tsujimoto T., Barnes-Davies M., Cuttle M.F., & Takahashi T. (1998). Inactivation of presynaptic calcium current contribute to synaptic depression at a fast central synapse. Neuron 20, 797-807. 

Takahashi T., Forsythe I., Tsujimoto T., Barnes-Davies M. & Onodera K. (1996). Presynaptic calcium current modulation by a metabotropic glutamate receptor. Science 274, 594- 597.

 Kobayashi K., Manabe T. & Takahashi T. (1996). Presynaptic long-term depression at the hippocampal mossy fiber-CA3 synapse. Science 273, 648-650.

 Farrant M., Feldmeyer D., Takahashi T. & Cull-Candy S.G. (1994). NMDA-receptor channel diversity in the developing cerebellum. Nature 368, 335-339.

 Hayashi Y., Momiyama A., Takahashi T., Ohishi H., Ogawa-Meguro R., Shigemoto R., Mizuno N. & Nakanishi S. (1993). Role of a metabotropic glutamate receptor in synaptic modulation in the accessory olfactory bulb. Nature 366, 687-690.

 Takahashi T. & Momiyama A. (1993). Different types of calcium channels mediate central synaptic transmission. Nature 366,156-158.

 Takahashi T., Momiyama A., Hirai K., Hishinuma F. & Akagi H. (1992). Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels. Neuron 9,1155-1161.

 Takahashi T. & Momiyama A. (1991). Single-channel currents underlying glycinergic inhibitory postsynaptic responses in spinal neurons. Neuron 7, 965-969.

 Edwards F.A., Konnerth A., Sakmann B. & Takahashi T. (1989). A thin slice preparation for patch clamp recordings from neurones of the mammalian central nervous system. Pflugers Arch. 414, 600-612. (Authours are in alphabetical order)

Takahashi T., Neher E. & Sakmann B. (1987). Rat brain serotonin receptors in Xenopus oocytes are coupled by intracellular calcium to endogenous channels. Proc. Natl. Acad. Sci. U. S. A. 84, 5063-5067.

Noda M., Ikeda T., Suzuki H., Takeshima H., Takahashi T., Kuno M.& Numa S. (1986). Expression of functional sodium channels from cloned cDNA. Nature 322, 826-828.

 Mishina M., Takai T., Noda M., Takahashi T., Numa S., Methfessel C. & Sakmann B. (1986). Molecular distinction between fetal and adult forms of muscle acetylcholine receptor. Nature 321, 406-411.

 Mishina M., Kurosaki T., Tobimatsu T., Morimoto Y., Noda M., Yamamoto T., Terao M., Lindstrom J., Takahashi T., Kuno M. & Numa S. (1984). Expression of functional acetylcholine receptor from cloned cDNAs. Nature 307, 604-608.

Eusebi F., Miledi R. & Takahashi T. (1980). Calcium transients in mammalian muscles. Nature 284, 560-561.