Development of Cortical Barrels in GAP-43 Deficient Mice

GAP-43 缺陷小鼠皮质桶的发育

• 批准号: 6529643
• 负责人: JAMES STACY MCCASLAND
• 金额: $ 30.4万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-15 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6529643
• 关键词: NMDA receptors; autoradiography; brain mapping; cerebral cortex; developmental genetics; developmental neurobiology; gene environment interaction; gene expression; gene mutation; genetically modified animals; histology; immunocytochemistry; intermolecular interaction; laboratory mouse; morphometry; neural growth associated protein; neural information processing; neural plasticity; neurogenetics; neuronal guidance; neurons; protein structure function; sensorimotor system; stimulus /response; synaptogenesis; western blottings

Maps of body surfaces are central to brain development and function. Yet the processes by which these maps form in cerebral cortex are very poorly understood. Understanding the mechanisms underlying cortical map development is the long-range goal of this research. Specific aims of this proposal are to: Determine if map dimensions are influenced by whisker activation in GAP-43 (+/-) barrel cortex. Determine if barrel dimensions are correlated with GAP-43 expression in (+/-) mice. Determine if barrel dimensions in GAP-43 (+/-) mice are NMDA receptor dependent. Determine if barrel maturation is delayed by reduced GAP-43 expression. We propose to answer these questions using as a model system a mouse line with reduced or no expression of Growth-Associated Protein (GAP-43 (+/-) and (-/-)). The power of our approach is demonstrated by our recent discovery of disrupted whisker/barrel maps in GAP-43 (-/-) cortex, and of enlarged barrels and activity-dependent barrel dimensions in GAP-43 (+/-) mice. The mature central nervous system is an extraordinarily complex arrangement of contacts between specialized cells. The precision of the array is necessary for function. Thus, the mechanisms of target selection and formation of stable connections are extremely important in developmental neurobiology. They are critical to understanding congenital abnormalities and dysplasias, and also in potential therapies to restore function after damage to the nervous system [1]. Our discovery of enlarged barrels and activity-dependent barrel dimensions in GAP- 43 (+/-) cortex creates a unique opportunity to dissect the processes of barrel formation. These studies can have a fundamental impact on our understanding of map development in cerebral cortex.

身体表面的地图是大脑发育和功能的核心。 然而，人们对这些地图在大脑皮层中形成的过程知之甚少。 了解皮层地图发展的机制是这项研究的长期目标。 本提案的具体目标是：确定地图尺寸是否受到GAP-43（+/-）桶皮质中晶须激活的影响。确定桶尺寸是否与（+/-）小鼠中的GAP-43表达相关。确定GAP-43（+/-）小鼠的桶尺寸是否具有NMDA受体依赖性。确定桶成熟是否因GAP-43表达减少而延迟。我们建议使用生长相关蛋白（GAP-43（+/-）和（-/-））表达减少或不表达的小鼠系作为模型系统来回答这些问题。 我们最近发现GAP-43（-/-）皮质中的晶须/桶图被破坏，以及GAP-43（+/-）小鼠中的桶扩大和活动依赖性桶尺寸，证明了我们方法的强大性。成熟的中枢神经系统是一个非常复杂的安排之间的联系专门的细胞。 数组的精度是函数所必需的。 因此，靶点选择和稳定连接形成的机制在发育神经生物学中是极其重要的。 它们对于理解先天性异常和发育不良以及神经系统损伤后恢复功能的潜在治疗至关重要[1]。 我们在GAP- 43（+/-）皮质中发现了扩大的桶和活动依赖的桶尺寸，这为解剖桶形成的过程创造了一个独特的机会。 这些研究可能对我们理解大脑皮层中的地图发展产生根本性的影响。