Department of Neurophysiology
Professor
Tomoyuki Takahashi, M.D., Ph.D.
Lecturer
Tetsuhiro Tsujimoto, M.D., Ph.D.
Associate
Katsunori Kobayashi, Ph.D.

Our laboratory was founded in 1953 as Department of Neurophysiology, Institute for Brain Research, and since 1996 integrated into Graduate School of Medicine. We are engaged in teaching neurophysiology to students in graduate and medical schools as well as in research for elucidating cellular and molecular mechanisms underlying synaptic functions.

Teaching activities
We teach medical undergraduates in lectures and a practical course. Lectures are designed for students to learn basic mechanisms underlying electrical signals, how they are produced and propagated through nerve fibers and across synapses. Students also learn dynamic aspects of synaptic efficacy underlying diverse brain functions such as memory and consciousness. Several months before lectures students in 20 groups are given key words with references to prepare a summary upon which each group presents a short talk in a class. Their talks are followed by discussions and supplementary lectures by instructors. During the procedure of preparations, students have chances to discuss with instructors. In practical course, students are encouraged to make patch-clamp recordings from neurons visually identified in thin brain slices under microscope. In this course, students learn how electrical signals are made of ion channel currents. In separate set-ups, students record field synaptic potentials from hippocampal slices and learn how synaptic efficacy can be modulated. Trainings for the master and doctor course students are made regularly on Monday in the forms of progress reports and journal clubs where students and staffs read very recent papers as well as classics in physiology and neuroscience.

Research Activities
Synapses in various CNS regions are not uniform in modulatory functions but have their own characteristics. Synaptic functions also undergo changes during postnatal development and in response to various kinds of stimulation. These diverse and dynamic aspects of synapses arise from distinct molecular compositions among synapses and their developmental switches. Our present aim is to clarify physiological roles of synaptic molecules in transmission and modulation. To this end, we apply electrophysiological, molecular and immunohistochemical techniques to central synapses visually identified in rodent brainstem slices. For example, we have developed a method to make patch-clamp recordings from a giant nerve terminal called the calyx of Held. At this synapse, the role of presynaptic molecules can be studied by loading their specific antibodies or inhibitory peptides into a nerve terminal through patch-pipettes while recording presynaptic and postsynaptic electrical signals simultaneously. Also, using immunohistochemical techniques and confocal optics, it is possible to follow translocation of presynaptic molecules upon stimulation. Information obtained from this preparation is compared with those from other central synapses at various developmental ages. Through these approaches taken together with results obtained from knockout mice, we attempt to clarify molecular basis for synaptic and brain functions.

References
  1. 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.
  2. Ishikawa T., Sahara Y., Takahashi T. (2002) A single packet of transmitter does not saturate postsynaptic glutamate receptors. Neuron 34, 613-621.
  3. Yamashita T., Ishikawa T., Takahashi T. (2003) Developmental increase in vesicular glutamate content dose not cause saturation of AMPA receptors at the calyx of Held synapse. Journal of Neuroscience 23, 3633-3638.
  4. Mori-Kawakami F., Kobayashi K., Takahashi T. (2003) Developmental decrease in synaptic facilitation at the mouse hippocampal mossy fiber synapse. Journal of Physiology (London) 553, 37-48.
  5. Ishikawa T., Nakamura Y., Saitoh N., Li W.B., Iwasaki S. & Takahashi T. (2003) Distinct roles of Kv1 and Kv3 potassium channels at the calyx of Held presynaptic terminal Journal of Neuroscience 23, 10445-10453.
  6. Kimura M., Saitoh N. & Takahashi T. (2003) Adenosine A1 receptor-mediated presynaptic inhibition at the calyx of Held of immature rats. Journal of Physiology (London) 553, 415-426.
Annual Report of the Graduate School of Medicine and The Faculty of Medicine The University of Tokyo Reports for the Period April 2002 - March 2004