| Project/Area Number |
15500274
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
KOIZUMI Schuichi Natl.Inst.Hlth.Sci., Div.Pharmacol., Lab Chief, 室長 (10280752)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | astrocytes / ATP / synapse / glia-to-neuron interaction / P2 receptor / Ca^<2+> wave / 脳血管 / グリア-ニューロン連関 / 三者間シナプス / 海馬 |
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| Research Abstract |
Originally ascribed passive roles in the CNS, astrocytes are now known to have an active role in the regulation of synaptic transmission. Neuronal activity can evoke Ca^<2+> transients in astrocytes and Ca^<2+> transients in astrocytes can evoke changes in neuronal activity. The excitatory neurotransmitter glutamate has been shown to mediate such bi-directional communication between astrocytes and neurons. We demonstrate here that ATP, a primary mediator of intercellular Ca^<2+> signaling among astrocytes, also mediates intercellular signaling between astrocytes and neurons in hippocampal cultures. Mechanical stimulation of astrocytes evoked Ca^<2+> waves mediated by the release of ATP and activation of P2 receptors. Mechanically evoked Ca^<2+> waves led to decreased excitatory glutamatergic synaptic transmission in an ATP-dependent manner. Exogenous application of ATP does not affect post-synaptic glutamatergic responses but decreased pre-synaptic exocytotic events. Finally, we show that astrocytes exhibit spontaneous Ca^<2+> oscillations mediated by extracellular ATP and that inhibition of these Ca^<2+> responses enhanced excitatory glutamatergic transmission. We therefore conclude that ATP released from astrocytes exerts tonic and activity-dependent down-regulation of synaptic transmission via pre-synaptic mechanisms.
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