My research life: From synaptic transmission to behavior

Abstract

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 purifed 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 junctionsby 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 Drosophilanerve terminals. We then identifed two Ca 2+ channels designated for the low- and high-frequency endocytosis of synaptic vesicles, straightjacket Ca 2+ channels in the active zone and La 3+ -sensitive Ca 2+ channels in the inactive zone at the terminals, respectively. Recently,Drosophila melanogasterhas been used as a model for studying the social brain, and the heat avoidance response of the flies was found to besocially enhanced. Future studies are expected to reveal mechanisms underlying social brain functions at the gene level. © 2014 The Pharmaceutical Society of Japan.