| Co-Investigator(Kenkyū-buntansha) |
SAMEJIMA Michikazu Seirei Christopher College, Nursing, Professor, 看護学部, 教授 (80135251)
FUKUDA Atsuo HAMAMATSU UNIVERSITY, Medicine, Physiology, Professor, 医学部, 教授 (50254272)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
GABA is the most principal inhibitory neurotransmitter in the brain. However, in the regulation of circadian rhythm, it is suggested that GABA shows the excitatory effect and plays an important role. In a living organism, physiological and behavioral parameters are known to be controlled by endogenous oscillators and to show a daily rhysmicity with a period of about 24h. The seat of the oscillator differs from species to species. In mammals, the suprachiasmatic nucleus (SCN) is widely accepted as the seat of the oscillator. In the visual system, it has been reported that GABA shows the excitatory effects on immature neurons in the retina and the visual cortex, hence inducing calcium influx. Thus, GABA is expected to have some trophic action in the process of the neuronal development. In this study, using optical imaging of [Cl]_i with 6-methoxy-N-ethylquinolinium iodide (MEQ) fluorescence, we have compared the effects of GABA on neuronal [Cl]_i changes in the SCN, the dorsal lateral geniculate nucleus (DLG), and the visual cortex (VC). In addition, we consider that differential regulational process of neuronal Cl^-homeostasis in those regions. Therefore, we examined the expession changes of cation-Cl^-cotransporters, e.g., outwardly directed K^+-Cl^-cotransporter KCC2 and inwardly directed Na^+,K^+-2Cl^-cotransporter NKCC1, in SCN, DLG and VC. The [Cl]_i and expression of NKCC1 mRNA of SCN neurons was higher in daytime than in nighttime. The application of vasopressin tended to downregulate [Cl]_i in daytime. And only in the immature VC, application of GABA elicited an increase in, indicating a decrease in [Cl]_i. In the P0 DLQ the expression of KCC2 mRNA signals were higher than that in VC. This suggests that extrusion of Cl^-from neuron is higher in the DLG than in the VC, so that GABAergic excitatory effect were not observed in DLG because of more negative equilibrium potential for Cl^-.
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