Development of Cortical Barrels in GAP-43 Deficient Mice

身体表面的地图是大脑发育和功能的核心。然而，这些地图在大脑皮层中形成的过程却知之甚少。了解皮层地图发育的机制是本研究的长期目标。该建议的具体目的是：确定地图尺寸是否受到GAP-43（+/-）桶状皮层中须状突激活的影响。确定桶尺寸是否与（+/-）小鼠的GAP-43表达相关。确定GAP-43（+/-）小鼠的桶形尺寸是否依赖于NMDA受体。确定是否通过降低GAP-43表达延迟桶成熟。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（-/-）皮层中发现了断裂的须/桶图，在GAP-43（+/-）小鼠中发现了增大的桶和活动依赖的桶尺寸，证明了我们方法的力量。成熟的中枢神经系统是特化细胞之间异常复杂的接触安排。数组的精度是函数所必需的。因此，目标选择和稳定连接的形成机制在发育神经生物学中非常重要。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。我们在GAP- 43（+/-）皮层中发现了增大的桶和与活动相关的桶尺寸，这为解剖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对大脑皮层地图发育的理解产生根本性的影响。

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.