| Project/Area Number |
15300104
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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 |
Neuroscience in general
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YAMAGUCHI Masahiro The University of Tokyo, Graduate School of Medicine, Lecturer, 大学院・医学系研究科, 講師 (60313102)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2003: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | olfactory bulb / granule cell / neurogenesis / nestin / GFP / GEP |
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| Research Abstract |
In the olfactory bulb (OB) of nestin-GFP transgenic mice produced in our lab, two types of GFP-expressing cells were observed. The cells with weak GFP expression (type W cells) were immature granule cells in the OB, and the cells with strong GFP (type S cells) were mature granule cells with characteristic morphologies.
1.Molecular analysis of integration of new neurons into preexisting neuronal circuit
By experimentally regulating the olfactory sensory input to mice, I revealed the existence of a critical period after the generation of new granule cells when their survival is crucially influenced by olfactory sensory experience (PNAS, 2005).
Following the establishment of neuronal circuit in vitro from dispersed cells of mouse OB, neurons derived from the nestin-GFP mouse OB were added. Then the GFP-expressing type W granule cells were found to be incorporated into the preexisting neuronal circuit. When the neuronal activity was inhibited by drug application to the culture, cell death of the immature granule cells were enhanced. Thus I have succeeded in establishing an in vitro system where mechanism of activity-dependent integration of new neurons into preexisting neuronal circuit can be effectively analyzed.
2.Identification of a novel type of perisomatic-targeting granule cells
Type S cells with strong GFP expression expressed GABA and other marker proteins for mature granule cells. By intracellular dye labeling, I found that the dendritic tips of type S cells contacted with soma of mitral cells, the excitatory projecting neurons of the OB. Electron microscopic analysis revealed the existence of reciprocal synapses at the contact sites. Type S cells were found to be a novel type of GABAergic inhibitory granule cells that send inhibition specifically to mitral cell soma through the reciprocal synaptic interactions (manuscript in preparation).
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