Experience Dependent Neocortical Development

描述(申请人提供)：我们研究的长期目标是了解体验如何影响特别感兴趣的皮质微回路的组织和发展，以及新生儿触觉体验如何影响大鼠躯体感觉皮质中与胡须相关的桶。我们以前的研究表明，正常的触觉体验对于建立皮质桶状神经元的正常反应特性是必不可少的。在出生后的最初几周，修剪胡须会增加桶状神经元的兴奋性，并使其感受野强劲而持久地扩大。然而，这些变化并不伴随着桶的地形模式或整体形态的变化。相反，现有的证据表明，这些生理异常反映了单个枪管内局部兴奋回路的变化。拟议的研究计划将详细研究皮质微回路的发展及其因异常触觉体验而发生的变化。这项研究的前提是，单个桶是由模块单元组成的，而新生儿的经验正是在这些微电路的层面上施加影响的。这些微电路现在可以用现代基于细胞的解剖学和生理学技术进行分析。实验旨在研究正常和胡须修剪大鼠的皮质微电路如何在结构和功能上与它们的传入输入相匹配。具体地说，我们将详细研究1)单个丘脑皮质轴突的树枝状分布模式，2)局部反复桶内连接的空间模式，以及3)兴奋性突触传递到个别桶状神经元的强度。通过将视觉系统研究的重要发现延伸到躯体感觉皮质，预期的结果将直接有助于识别皮层发育背后的活动依赖过程的一般原理。了解这些原理及其作用的细胞机制对于最终诊断、治疗和预防影响知觉、认知和其他高级皮质功能的发育障碍至关重要。

DESCRIPTION (provided by applicant): The long-term goal of our research is to understand how experience influences the organization and development of cortical microcircuits Of particular interest is how neonatal tactile experience influences whisker-related barrels in the rat somatosensory cortex. Our previous studies demonstrate that normal tactile experience is essential for the establishment of normal response properties of cortical barrel neurons. Trimming whiskers for the first few postnatal weeks leads to increased excitability of barrel neurons and to a robust and permanent enlargement of their receptive fields. These changes are not, however, accompanied by changes in the topographic pattern or overall morphology of barrels. Instead, available evidence indicates that these physiological abnormalities reflect alterations in local excitatory circuits within individual barrels.The proposed research plan will investigate in detail the development of cortical microcircuits and their alteration by abnormal tactile experience. The research is based on the premise that individual barrels are composed of modular units, and it is at the level of these microcircuits that neonatal experience exerts its influence. These microcircuits are now amenable to analysis using modern cellular-based anatomical and physiological techniques.Experiments are designed to investigate, in normal and whisker-trimmed rats, how cortical microcircuits become matched structurally and functionally to their afferent inputs. Specifically, we will examine in detail 1) the arborization pattern of individual thalamocortical axons, 2) the spatial pattern of locally recurrent intra-barrel connections, and 3) the strength of excitatory synaptic transmission onto individual barrel neurons.Results of the proposed research will provide insight into developmental mechanisms that organize local cortical circuits. By extending, to the somatosensory cortex, important findings from investigations of the visual system, the anticipated results will contribute directly to the identification of general principles of activity-dependent processes underlying cortical development. An understanding of these principles and the cellular mechanisms through which they operate is essential for the eventual diagnosis, treatment and prevention of developmental disorders affecting perception, cognition and other higher cortical functions