| Project/Area Number |
11670036
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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 |
General physiology
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| Research Institution | Kanazawa Uiversity |
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Principal Investigator |
OHNO-SHOSAKU Takako Kanazawa University, Fac.of Med., assistant professor, 医学部, 助教授 (60179025)
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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 |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Retrograde signal / Cannabinoid receptor / Synaptic modulation / Inhibitory synaptic transmission / Hippocampus / グリア / 抑制性シナプス / シナプス伝達調整 |
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| Research Abstract |
1.Recent studies have suggested that retrograde messengers might play an important role in synaptic modulations and plasticity in the central nervous system. In the hippocampus, depolarization of a CA1 pyramidal neuron elicits a transient suppression of inhibitory synaptic inputs to the depolarized cell. This phenomenon is referred to as DSI (depolarization-induced suppression of inhibition). The studies with hippocampal slices demonstrated that a retrograde messenger should be involved in DSI.
2. To identify the retrograde signal of DSI, we made a paired whole-cell recording from cultured rat hippocampal neurons with inhibitory synaptic connections, and examined the properties of the inhibitory transmission and DSI.In about 60% of pairs, a cannabinoid agonist greatly reduced the release of the inhibitory transmitter GABA from presynaptic terminals. In most of such pairs but not in those insensitive to the agonist, depolarization of postsynaptic neurons and the resultant elevation of intracellular Ca^<2+> concentraton caused transient suppression of inhibitory synaptic currents (DSI), which is mainly due to reduction of GABA release. This DSI was completely blocked by cannabinoid receptor antagonists. The data indicate that endogenous cannabinoids mediate the retrograde signal of DSI.
3. These and our previous results support the following hypothesis accounting for DSI.Depolarization of a postsynaptic neuron elicits an increase in postsynaptic intracellular Ca^<2+> concentration by activating Ca^<2+> channels, which in turn triggers the biosynthesis and release of endogenous cannabinoids. The released cannabinoids bind to presynaptic cannabinoid receptors, and their activation suppresses the transmitter release from inhibitory presynaptic terminals.
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