Development of Cortical Barrels in GAP-43 Deficient Mice

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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.