| Project/Area Number |
11670116
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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 medical chemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
WATANABE Dai Kyoto University, Instructor Department of Biological Sciences, 医学研究科, 助手 (90303817)
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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: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | transgenic mouse / interneuron / glutamate / 小脳 / GABA / イムノトキシン |
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| Research Abstract |
We generated transgenic mice that expressed human interleukin-2 receptor alpha subunit fused to green fluorescent protein(GFP)under the control of the mGluR2 promoter. Consistent with specific mGluR2 expression, double immunostaining showed the complete overlap of GFP-positive cells with choline acetyltransferase(ChAT)-immunoreactive interneurons in both striatum and retina.
1.The physiological role of striatal cholinergic intemeurons was investigated with immunotoxin-mediated cell targeting(IMCT). Unilateral cholinergic cell ablation caused an acute abnormal turning behavior. These mice showed gradual recovery but displayed abnormal turning by both excess stimulation and inhibition of dopamine actions. In the acute phase, basal ganglia function was shifted to a hyperactive state by stimulation and suppression of striatonigral and striatopallidal neurons, respectively. D1 and D2 dopamine receptors were then down-regulated, relieving dopamine-predominant synaptic perturbation but leaving a defect in controlling dopamine responses. The acetylcholine-dopamine interaction is concertedly and adaptively regulated for basal ganglia synaptic integration.
2.The directional selectivity of retinal ganglion cell responses represents a primitive pattern recognition that operates within a retinal neural circuit. The cellular origin and mechanism of directional selectivity were investigated by selectively eliminating retinal cholinergic interneurons, namely starburst cells, using lMCT.Starburst cell ablation in the adult retina abolished not only directional selectivity of ganglion cell responses but also an optokinetic eye reflex derived by stimulus movement. Starburst cells therefore serve as the key element that discriminates the direction of stimulus movement through integrative synaptic transmission and play a pivotal role in information processing that stabilizes image motion.
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