Development of Cortical Barrels in GAP-43 Deficient Mice

GAP-43 缺陷小鼠皮质桶的发育

• 批准号: 6774748
• 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 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6774748
• 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.

身体表面的地图对大脑的发育和功能至关重要。然而，这些地图在大脑皮层中形成的过程却知之甚少。了解大脑皮层地形图形成的机制是本研究的长期目标。这项提议的具体目的是：确定MAP的维度是否受到GAP-43(+/-)桶状皮质中胡须激活的影响。确定枪管尺寸是否与(+/-)小鼠的GAP-43表达相关。确定GAP-43(+/-)小鼠的枪管尺寸是否依赖NMDA受体。确定是否由于GAP-43表达减少而延迟了管状细胞成熟。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。我们最近在GAP-43(-/-)皮质中发现了中断的胡须/桶图，在GAP-43(+/-)小鼠中发现了扩大的桶和活动依赖的桶尺寸，这证明了我们方法的力量。成熟的中枢神经系统是特殊细胞之间联系的异常复杂的安排。阵列的精度是实现功能所必需的。因此，靶点选择和稳定连接的形成机制在发育神经生物学中是极其重要的。它们对于了解先天性异常和发育不良，以及在神经系统受损后恢复功能的潜在疗法中都是至关重要的[1]。我们在GAP-43(+/-)皮质中发现了扩大的桶和依赖活动的桶尺寸，这为剖析桶的形成过程创造了一个独特的机会。这些研究可以对我们理解大脑皮层MAP的发展产生根本性的影响。

项目成果

Resistance to change and vulnerability to stress: autistic-like features of GAP43-deficient mice.

• DOI: 10.1111/j.1601-183x.2010.00638.x
• 发表时间: 2010-11
• 期刊: Genes, brain, and behavior
• 作者: Zaccaria KJ;Lagace DC;Eisch AJ;McCasland JS
• 通讯作者: McCasland JS