| Project/Area Number |
12210014
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | OSAKA UNIVERSITY |
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Principal Investigator |
TSUMOTO Tadaharu Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (50028619)
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| Co-Investigator(Kenkyū-buntansha) |
UCHIYAMA Yasuo Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (10049091)
SOBUE Kenji Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (20112047)
山本 宣彦 大阪大学, 基礎工学研究科, 助教授 (00191429)
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| Project Period (FY) |
2000 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥108,900,000 (Direct Cost: ¥108,900,000)
Fiscal Year 2004: ¥26,400,000 (Direct Cost: ¥26,400,000)
Fiscal Year 2003: ¥26,400,000 (Direct Cost: ¥26,400,000)
Fiscal Year 2002: ¥26,400,000 (Direct Cost: ¥26,400,000)
Fiscal Year 2001: ¥29,700,000 (Direct Cost: ¥29,700,000)
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| Keywords | Cerebral Cortex / Visual Cortex / Development / Brain-Derived Neurotrophic Factor / Synaptic Plasticity / GABAergic Neuron / Green Fluorescence Protein / Long-term Depression / 神経栄養因子 / 抑制性シナプス / 細胞移動 / 緑色蛍光蛋白質 / カテプシン / 眼優位円柱 / シナプス / カテプシンD |
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| Research Abstract |
In this research project we attempted to elucidate a role of brain-derived neurotrophic factor (BDNF) in development of neuronal circuits of the cerebral cortex. In 2000 and 2001, we investigated a possible contribution of BDNF in formation of ocular dominance (OD) columns in kitten visual cortex, and found that BDNF expands the size of OD columns. Also, we found that BDNF is released from presynaptic neurons and transferred to postsynaptic neurons in an activity-dependent manner. In 2002 we studied a possible involvement of BDNF in long-term depression (LTD) of synaptic transmission in visual cortex. We found that BDNF, which was exogenously applied to visual cortical slices prevented prolonged, low-frequency stimulation (LFS) of afferents from inducing LTD at synapses of cortical layer II/III neurons. Also we found that in the more physiological in vivo condition, LFS did not induce LTD because of the presence of endogenous BDNF in visual cortex. In 2003 and 2004 we tested whether BDNF has any action on development of GABAergic, inhibitory neurons using neuron culture preparations or visual cortical slices of GAD67-GFP knock-in mice. We found that BDNF promotes morphological and functional development of postsynaptic, GABAergic neurons. Because GABAergic neurons cannot produce BDNF by themselves and thus depends on BDNF which is transferred from other excitatory neurons in an activity dependent manner, the dependency of development of immature neuronal circuits on neuronal activity is ascribable mostly if not all to the dependency of development of GABAergic neurons on BDNF.
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