| Project/Area Number |
16300134
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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 |
Neurophysiology and muscle physiology
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| Research Institution | Tokyo Metropolitan Institute of Gerontology |
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Principal Investigator |
AOSAKI Toshihiko Tokyo Metropolitan Institute of Gerontology, Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Tokyo Metropolitan Institute of Gerontology, Team Sub-leader, Group Leader (70221033)
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| Project Period (FY) |
2004 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥15,780,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2007: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | striatum / compartments / dopamine / striosome / matrix / talamus / acetylcholine / functional module / GFP / トランスジェニックマウス / オビオイド / 大脳基底核 / FS細胞 / パッチクランプ |
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| Research Abstract |
We studied how the information was processed in the striatal local circuits and how the thalamic inputs to the striatum regulated the striatal outputs. Our in vitro electrophysiological study using brain slice preparation revealed that a type of inhibitory GABAergic interneuron called fast-spiking interneuron (FS cell)innervated numerous output neurons, forming minimum functional modules. These minimum units of functional modules were innervated and grouped further by another type of GABAergic interneuron called low-threshold spiking cell (LTS cell) and cholinergic interneuron. Among these interneuronal types thalamostriatal synapses are known to be formed on cholinergic interneurons. They are frequently locates between striosomes/patches and the extrastriosomal matrix compartment of the striatum. The striosome compartments are rich in μ opioid receptors which are activated by enkephalin released by indirect pathway output neurons. We found that activation of μ opioid receptors suppres
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sed inhibitory postsynaptic current (IPSCs) on output neurons and cholinergic interneurons in the striosomes, which would in turn promote excitation of cholinergic interneurons triggered by thalamic excitatory inputs. Cholinergic interneurons released acetylcholine which then excited FS interneurons. Therefore, activation of indirect pathway output neurons in the striosome compartments would suppress activity of minimum functional units via cholinergic interneurons. In summary, during motor learning cholinergic interneurons receive thalamic excitatory inputs and nigrostriatal dopaminergic inputs. Dopamine neurons excite and release dopamine, while cholinergic interneuron suppress tonic firing at the time of sensory cue presentation. Recent reports indicate that without nicotinic receptor activation the amount of released dopamine is dramatically high. It is also reported that without muscarinic receptor activation corticostriatal post synaptic excitatory potential (EPSP) would be larger. Suppression of functional units by FS interneurons via nicotinic receptor activation would be relieved at the time of learning only in the area where the suppressed cholinergic interneuron innervates. Therefore, high amount of dopamine, larger EPSP and relief from GABAergic suppression might facilitate plastic changes in output neurons in the area, leading to acquisition of a novel behavioral pattern. Less
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