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: 7086847
• 负责人: MICHAEL P STRYKER
• 金额: $ 18.82万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7086847
• 关键词: biological signal transduction; brain derived neurotrophic factor; calmodulin dependent protein kinase; developmental neurobiology; genetically modified animals; growth factor receptors; intercellular connection; laboratory mouse; neocortex; neural plasticity; neurogenetics; neurotrophic factors; protein kinase A; serotonin; visual cortex; visual deprivation; visual pathways

To study the factors that regulate synaptic connections in the developing neocortex, the Stryker laboratory will study transgenic mice with targeted disruptions of genes whose products are involved in synaptic plasticity. The major research goals are (1) to delineate the role of TrkB neurotrophin signaling in activity-dependent plasticity in the visual cortex, using mice defective in TrkB in specific populations of neurons and mice in which the expression of BDNF is temporally regulated; (2) to determine the role of the autophosphorylation and possible dendritic synthesis of calcium calmodulin kinase type II in the induction and maintenance of activity-dependent plasticity in the visual cortex using transgenic mice defective in these processes, and (3) to survey the roles of a number of molecules important for neuronal pathfinding and specification of cortical topography using a novel mapping technique to measure the size and topographic organization of primary visual cortex and 4 higher cortical visual areas in inducible transgenic knockout mice. We expect that if the roles of these molecules turn out to be important and more than merely permissive in activity-dependent plasticity, the new understanding of cortical plasticity would have important implications for our understanding of common neurodevelopmental abnormalities and hence for candidate therapies.

为了研究调节发展中新皮层突触连接的因素，Stryker 实验室将研究具有涉及突触可塑性的基因的靶向破坏的转基因小鼠。主要的研究目标是（1）描述TRKB神经营养蛋白信号传导在视觉皮层中活性依赖性可塑性中的作用，使用在特定的神经元和小鼠中有缺陷的小鼠BDNF表达在时间上受到临时调节的小鼠； (2) to determine the role of the autophosphorylation and possible dendritic synthesis of calcium calmodulin kinase type II in the induction and maintenance of activity-dependent plasticity in the visual cortex using transgenic mice defective in these processes, and (3) to survey the roles of a number of molecules important for neuronal pathfinding and specification of cortical topography using a novel mapping technique to measure the size and地形 在诱导的转基因敲除小鼠中的一级视觉皮层和4个高层皮质视觉区域的组织。我们预计，如果这些分子的作用变得重要，并且不仅仅是在活性依赖性可塑性方面允许的，那么对皮质可塑性的新理解将对我们对常见神经发育异常的理解以及候选疗法具有重要意义。