The role of tissue-type plasminogen activator in visual cortical plasticity

组织型纤溶酶原激活剂在视觉皮层可塑性中的作用

• 批准号: 11480243
• 负责人: HENSCH Takao
• 金额: $ 9.34万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11480243/
• 关键词: 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

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.

丝氨酸蛋白酶、组织型纤溶酶原激活剂 (tPA) 是细胞外蛋白水解级联的关键调节剂。我们证明了小鼠视觉皮层在发育关键期的经验依赖性可塑性对 tPA 信号传导的需求。双眼区域中 tPA 的蛋白水解活性通常在单眼剥夺 (MD) 两天内增加。这种调节在谷氨酸脱羧酶 (GAD) 65 基因敲除小鼠中未能发生，这是一种由于先前描述的 GABA 能传递减少而导致眼部优势可塑性受损的动物模型。相反，尽管神经元活动水平正常，但缺乏 tPA 的小鼠中，MD 导致的失眼反应性丧失却受到抑制。可塑性以基因剂量依赖性方式恢复，或通过直接 tPA 输注。因此，允许量的 tPA 可能会将兴奋-抑制平衡下游的功能性结构变化耦合起来，从而触发视觉皮层可塑性。我们的结果不仅支持了感觉剥夺后导致神经突生长的分子级联反应，而且还确定了一种有价值的工具，可用于进一步对电活动下游的经验依赖性可塑性进行蛋白质组学和基因组解剖。

项目成果

Mataga,N.Nagai,N,Fujishima.S,Hensch.T.K.: "Disruption of experience-dependent plasticity in visual cortex in the absence of tissue-type plasminogen activator"Xlth International Congress on Fibrinolysis and Proteo lysis.. s117 (2000)

Mataga,N.Nagai,N,Fujishima.S,Hensch.T.K.：“在缺乏组织型纤溶酶原激活剂的情况下，视觉皮层中经验依赖性可塑性的破坏”第 X1 届国际纤维蛋白溶解和蛋白质溶解大会.. s117 (2000)

Matega, N. & Hensch, T.K: "A role for tissue-type plasminogen activator in ocular dominance plasticity in mouse visual cortex (II)"Neuroscience Research Supplement. 26 (in press).

马特加，N.

Mataga, N., Nagai, N., Fujishima, S., Hensch, T.K: "A role for tissue-type plasminogen activator in the experience-dependent plasticity of visual cortex"Neuroscience Research Supplement. 24. 54 (2000)

Mataga, N.、Nagai, N.、Fujishima, S.、Hensch, T.K：“组织型纤溶酶原激活剂在视觉皮层经验依赖性可塑性中的作用”神经科学研究增刊。

Mataga,N.,Fujishima,S Nagai,N.,Hensch T.K.: "Permissive levels of tissue-type plasminogen activator for experience-dependent plasticity in visual costex"Society for Neuroscience. 26. 856 (2000)

Mataga，N.，Fujishima，S Nagai，N.，Hensch T.K.：“视觉成本中经验依赖性可塑性的组织型纤溶酶原激活剂的允许水平”神经科学学会。

Mataga, N., Fujishima, S., Nagai, N., Hensch, T.K: "Physiological tissue-type plasminogen activator levels for experience-dependent plasticity"Society for Neuroscience. 27. B-25 (2001)

Mataga, N.、Fujishima, S.、Nagai, N.、Hensch, T.K：“经验依赖性可塑性的生理组织型纤溶酶原激活剂水平”神经科学学会。