| Project/Area Number |
11480243
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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 Institute of Physical and Chemical Research |
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Principal Investigator |
HENSCH Takao Neunonal function Group, Group Director, ニューロン機能研究グループ, グループディレクター (60300878)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Nobuo Hamamatsu University School of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (89716234)
OKUMURA Nobuaki Osaka University, Institute for Protein Research,Instructor, 蛋白質研究所, 助教授 (20224173)
MATAGA Nobuko Neuronal Circuit Development, Research Specialist, 神経回路発達研究チーム, 専門職研究員 (20209464)
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| Project Period (FY) |
1999 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | Plasminogen activator / Morphological changes / Critical Period / Monocular Deprivation / Ocular dominance plasticity / Binocular zone / Visual Cortex / Knockout mice / Western Blot Analysis / グルタミン酸脱炭酸酵素 / 単一神経細胞記録 / 神経活動依存性 / 大脳皮質第一次視覚野 / 機能欠失変異マウス |
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| Research Abstract |
The serine protease, tissue-type plasminogen activator (tPA) is a key regulator of extracellular proteolytic cascades. We demonstrate a requirement for tPA signaling in the experience-dependent plasticity of mouse visual cortex during the developmental critical period. Proteolytic activity by tPA in the binocular zone was typically increased within two days of monocular deprivation (MD). This regulation failed to occur in glutamic acid decarboxylase (GAD) 65 knockout mice, an animal model of impaired ocular dominance plasticity due to reduced GABAergic transmission described previously. Loss of responsiveness to the deprived eye consequent to MD was conversely suppressed in mice lacking tPA despite normal levels of neuronal activity. Plasticity was restored in a gene dose-dependent manner, or by direct tPA infusion. Permissive amounts of tPA may, thus, couple functional to structural changes downstream of the excitatory-inhibitory balance that triggers visual cortical plasticity. Our results not only support a molecular cascade leading to neurite outgrowth following sensory deprivation, but also identify a valuable tool for further proteomic and genomic dissection of experience-dependent plasticity downstream of electrical activity.
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