| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Mechanism underlying synaptic exocytosis has not been revealed yet, though many kinds of genes of proteins relating to exocytosis have been cloned and these amino acid sequences have been deduced. To investigate the physiological role of syntaxin 1A, a key protein for synaptic exocytosis, antibody against syntaxin 1A was applied into cell soma of the cultured rat hippocampal neuron through a whole cell patch-pipette in the present project. First, we analyzed effects of anti-syntaxin 1A antibody on the autaptic transmission of hippocampal neuron. Intracellular application of the antibody enhanced the autaptic transmission, that is, antibody against syntaxin lA enhanced the amplitude of the autaptic EPSC, while it did not change the asynchronous EPSC amplitude distribution. Quantal size of asynchronous EPSC was not affected by antibody. This result indicated that the antibody did not enhanced sensitivity of glutamate receptors located on the postsynaptic membrane, but it enhanced neurotransmitter release from the presynaptic terminal. This result suggested a suppressive role for syntaxin 1A in exocytosis at the mammalian central synapse. Second, to elucidate the modulatory mechanism of the synaptic exocytosis, the dependence of EPSC amplitude and paired pulse modification (ppm) on extracellular Ca^<2+> concentration was analyzed using the autapse of the cultured rat dentate neuron. Increase in cAMP concentration by forskolin caused enhancement of synaptic exocytosis Without changing ppm, suggesting principal reason of the enhancement of the synaptic exocytosis by forskolin from dentate neuron was increase in the size of docked vesicle pool (readily releasable pool) or number of release sites. This mechanism would play an important role in long-term potentiation of synaptic exocytosis at CA3 of mammalian hippocampus.
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