Experience Dependent Neocortical Development

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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