Yakugaku Zasshi 2014 Jan 01;1348:851-66. doi: 10.1248/yakushi.14-00151.

[My research life: from synaptic transmission to behavior].

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I have studied signal transmission at synapses and the effects of drugs on it at the molecular and cellular levels. Specific areas of research interest are outlined here. 1) Electrophysiological experiments in cats and rabbits suggested that a new type of analgesic, the phenothiazine derivative levomepromazine, exerts analgesic effects by depressing emotional responses accompanying the sensation of pain. 2) It was hypothesized that motoneurons had long-term effects on muscle cell membrane properties, in addition to controlling moment-to-moment activities. The substance to recover the post-denervation changes in muscle properties in culture was partially purified from mouse nerve extract, which suggested that trophic influences were exerted by substances released from motoneurons. 3) Muscles innervated by adrenergic fibers had sites responsive to acetylcholine as well as to adrenaline in early life in chicks, but only the adrenaline-responsive sites remained during development. Acetylcholine receptor clusters on Xenopus muscles were concentrated at the cholinergic neuromuscular junctions by the movement of receptors from outside the junctions during development. The passive diffusion-trap mechanism explained the accumulation of synaptic receptors at synapses. 4) We found two endocytic pathways and pools of synaptic vesicles contributing to low- and high-frequency synaptic transmission at Drosophila nerve terminals. We then identified two Ca2+ channels designated for the low- and high-frequency endocytosis of synaptic vesicles, straightjacket Ca2+ channels in the active zone and La3+-sensitive Ca2+ channels in the inactive zone at the terminals, respectively. Recently, Drosophila melanogaster has been used as a model for studying the social brain, and the heat avoidance response of the flies was found to be socially enhanced. Future studies are expected to reveal mechanisms underlying social brain functions at the gene level.

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