| Project/Area Number |
16300127
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Waseda University |
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Principal Investigator |
KONISHI Shiro Waseda University, Bioscience Institute, Professor (20014277)
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| Co-Investigator(Kenkyū-buntansha) |
SONG Si-Young Waseda University, Principal Investigator (00399693)
村越 隆之 東京大学, 大学院・総合文化研究所, 助教授 (60190906)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2005: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2004: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | GABAergic synapse / Purinoceptor / AMPA type glutamate receptor / Inhibitory synapse / Cerebellum / Purkinie cell / Basket cell / Climbing fiber / 神経伝達物質と受容体 / 神経情報処理 |
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| Research Abstract |
This research project had been performed based on the outcome from the CREST project supported by JST for "Pursuit of molecular mechanisms for plasticity at inhibitory GABAergic synapses". Previously we found novel forms of regulatory mechanisms for plasticity at inhibitory GABAergic synapses. This study therefore aimed to further examine details of regulatory mechanisms behind the multiple forms of synaptic plasticity at GABAergic synapses. We planned to study the following issues:
1. Search for cellular and molecular mechanisms underlying the regulation of GABAergic transmission.
1-(1) Monoaminergic short-term and long-term enhancement of GABAergic transmission.
1-(2) AMPA-type glutamate receptor-mediated presynaptic inhibition of GABAergic transmission.
1-(3) Origin of ATP that induces long-term increase of GABA receptor sensitivity via postsynaptic mechanism.
2. Search for therapeutic targets related to modulation at inhibitory GABAergic synapses.
We had investigated these issues and obtained results summarized below:
1. We found that ATP elicits a long-lasting enhancement of GABAergic transmission via activation of P2Y purinoceptors on postsynaptic Purkinje cells.
2. We demonstrated that there occur AMPA-type glutamate receptors in the nerve terminals of GABAergic interneurons, basket cells.
Activation of these receptors was shown to cause presynaptic inhibition, namely inhibition of GABA release from basket cell terminals.
3. Glutamate transpoter, EAAT4, was shown to control the AMPA receptor-mediated preysnpatic inhibition.
4. We constructed an assay system to visualize inhibitory GABAsergic synapses using VGAT-Venus transgenic mice for labeling
presynaptic terminals of GABAergic neurons and mCherry-labeled scaffolding protein for GABAA receptors.
Some of these resulted have been publishes as indicated in the reference list.
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