Development of Sensory maps in the Mammalian neocortex

描述(申请人提供)：这个项目的长期目标是了解大脑皮层感觉图形成的分子机制。我们目前的重点是验证这一假设，即丘脑皮质投射和新皮质之间的相互作用负责在新皮质形成特定区域和地形图的感觉图。在具体目标1中，我们将描述丘脑皮质投射与解剖和分子上不同区域的形成之间的时空关系，这是检验上述假设的关键第一步。在特定的目标2中，通过使用条件基因打靶，我们将分析丘脑皮质投射在建立新皮质的区域特异性特征中的作用。意义：对丘脑皮质轴突和分化的新皮质之间的相互作用的研究一直受到限制，因为缺乏可重复的实验系统来专门操作这两个组件中的任何一个。我们将使用小鼠的条件分子遗传学技术来探索这些相互作用。这项研究将对可能涉及丘脑皮质系统的发育障碍的病理生理学提供洞察力。此外，更好地了解感觉输入在大脑回路的发育和可塑性中的作用，将改进治疗干预措施，以操纵活动，鼓励患有脑损伤的儿童和成人的代偿性变化。

DESCRIPTION (provided by applicant): The long-term goal of this project is to understand the molecular mechanisms for the formation of sensory maps in the cerebral cortex. Our current focus is to test the hypothesis that reciprocal interactions between the thalamocortical projections and the neocortex are responsible for the formation of area-specific and topographic sensory maps in the neocortex. In Specific aim 1, we will characterize the spatiotemporal relationship between the thalamocortical projections and the formation of anatomically and molecularly distinct areas, which is a critical first step to test the above hypothesis. In Specific aim 2, by using conditional gene targeting, we will analyze the roles of thalamocortical projections in establishing area-specific features o the neocortex. SIGNIFICANCE:Studies of the interactions between the thalamocortical axons and the differentiating neocortex have been limited because of the lack of reproducible experimental systems to specifically manipulate either of the components. We will use conditional molecular genetic techniques of the mouse to explore these interactions. This study will provide insight into the pathophysiology of developmental disorders that may involve the thalamocortical system. In addition, a better understanding of the roles of sensory inputs in the development and plasticity of brain circuitry will improve therapeutic interventions to manipulate activity to encourage compensatory changes in both children and adults with brain damage.