| Project/Area Number |
11480244
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
神経・脳内生理学
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| Research Institution | GUNMA UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
KIDOKORO Yoshiaki Gunma University School of Medicine Institute for Behavioral Sciences, Division of Physiology Professor, 医学部, 教授 (00053083)
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| Co-Investigator(Kenkyū-buntansha) |
斎藤 実 群馬大学, 医学部, 助手 (50261839)
吉原 基二郎 群馬大学, 医学部, 助手 (80222397)
SAKAI Takaomi Gunma University School of Medicine Institute for Behavioral Sciences, Division of Physiology Research Associate (50322730)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 2000: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1999: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | synaptic transmission / Drosophila / mutants / patch-clamp / synaptobrevin / neuromuscular junctions / metabotropic glutamate receptors / synaptic vesicle pools |
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| Research Abstract |
i) Role of neuronal synaptobrevin (n-syb) for synaptic transmission. We examined synaptic transmission in Drosophila embryos lacking n-syb. No nerve-evoked synaptic currents were observed, but miniature synaptic currents (mSCs) were readily detected. The frequency of mSCs was Ca^<2+> dependent. Cyclic AMP did not increase the frequency of mSCs in the absence of external Ca^<2+>.
ii) Two independent pathways mediated by cAMP/PKA enhance spontaneous transmitter release at Drosophila neuromuscular junctions. We demonstrated that cAMP enhances synaptic transmission in the n-syb dependent and independent ways.
iii) Activation of metabotropic glutamate receptors enhances synaptic transmission at the Drosophila neuromuscular junction. Puff application of glutamate in Ca^<2+> -free saline increased the frequency of spontaneous synaptic currents. This response was blocked by antagonists of metabotropic glutamate receptors. Adenylyl cyclase activators, such as forskolin, mimicked the effect of glu
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tamate. The effect of glutamate was blocked by an inhibitor of adenylyl cyclase. In the presence of external Ca^<2+>, an agonist of metabotropic glutamate receptors enhanced synaptic transmission. At the larval Drosophila neuromuscular junction endogeneous glutamate released at the terminal potentiates synaptic transmission via a process involving cAMP.
iv) Screening for synaptic defects revealed a locus involved in presynaptic and postsynaptic functions in Drosophila embryos. A new mutant was isolated which has moderate defects in synaptic transmission. The gene was cloned and found to be identical to a recently reported gene, apontic, which presumably produces a transcription factor.
v) Two synaptic vesicle pools were identified at the Drosophila presynaptic terminal. The exo/endo cycling pool (readily releasable pool) is in the periphery of synaptic terminals and maintains synaptic transmission during low frequency stimulation, while vesicles in the reserve pool are released during high frequency stimulation. The size of the exo/endo cycling pool is proportionately related to the quantal content of synaptic transmission.
vi) Ultrastructure correlates of neuromuscular junction development. Ultrastructures of neuromuscular junction was examined in EM during early stages of synapse formation. Less
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