NEUROTROPHIN AND PROTEIN KINASE A SIGNALING IN NEOCORTICAL PLASTICITY

新皮质可塑性中的神经营养因子和蛋白激酶 A 信号传导

• 批准号: 6359664
• 负责人: MICHAEL P STRYKER
• 金额: $ 14.82万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6359664
• 关键词: developmental neurobiology; genetically modified animals; growth factor receptors; intercellular connection; laboratory mouse; neural plasticity; neurogenetics; neurotrophic factors; protein kinase A; serotonin; visual cortex; visual deprivation; visual pathways

This project proposes to develop further a transgenic mouse model of neocortical plasticity in order to investigate the roles of neurotrophins and their receptors, protein kinase A and downstream pathways and serotonin systems in the form of activity-dependent neural plasticity that refines thalamocortical and connections during normal development. In preliminary work, we have already established that many aspects of the physiological plasticity of the developing mouse visual cortex are similar to those in the cat, monkey, ferret, and human that we and others have studied earlier. In all these species, similar competitive interactions between inputs from the two eyes regulate, in an activity-dependent fashion, the relative strength of those inputs (referred to as ocular dominance), and this plasticity is observed only during a well-defined critical period in early life. In the mouse, as in the other species, we have delineated the critical period and have now shown that a brief period of monocular visual occlusion during the critical period results in the loss of responsiveness to the deprived eye and a complementary increase in cortical responses to the open eye; while a similar period of bilateral occlusion has no effect. The present proposal is to build upon this preliminary work to determine whether deletions of genes needed for models of adult plasticity in vitro also alter this form of developmental plasticity thought to be responsible for organizing neuronal connections to and within the developing visual cortex.

该项目建议进一步开发一个转基因鼠标模型 新皮层可塑性是为了研究神经营养蛋白的作用 及其受体，蛋白激酶A和下游途径以及 血清素系统以活动依赖性神经可塑性形式 在正常发育过程中优化丘脑皮质和连接。在 初步工作，我们已经确定了 发育中的小鼠视觉皮层的生理可塑性相似 对于我们和其他人的猫，猴子，雪貂和人类的人来说 先前研究。在所有这些物种中，类似的竞争互动 在两只眼睛的输入之间，在活动依赖性方面调节 时尚，这些投入的相对强度（称为眼 优势），并且仅在定义明确的情况下观察到这种可塑性 早期的关键时期。在鼠标中，就像其他物种一样，我们 已经描述了关键时期，现在已经表明了很短的一段时间 在关键时期的单眼视觉遮挡导致 丧失对被剥夺眼睛的反应能力和互补的增加 对睁大眼睛的皮质反应；而双边的类似时期 闭塞没有作用。目前的提议是基于此的 初步工作以确定模型所需的基因缺失 体外成人可塑性也改变了这种形式的发展 被认为负责组织神经元连接的可塑性 在开发的视觉皮层中。