The proposed studies will identify and characterize axon-dendrite interactions critical to development of the barrel neuron pattern in the murine primary somatosensory cortical representation of the mystacial vibrissae. Thalamic axons terminate selectively in the centers of the barrels. Granule neurons are concentrated at the define the sides of the barrels; each barrel neuron has several somatic dendrites oriented primarily toward the hollow of the respective barrel. Multiple morphologic methods including orthograde and retrograde axonal tracing techniques, single thalamic fiber HRP axonography and electron microscopy of identified axons will be used to determine the temporal and spatial patterns of entry of thalamocortical axons into the barrels, to characterize individual thalamic axon arbors and to define the composition of axon-dendrite compartments during synaptogenesis and barrel formation. The sequence of dendritic differentiation of barrel neurons will be reconstructed from plastic-embedded sections stained with monoclonal antibodies detecting the cytoskeleton protein MAP2 that is specific for neuronal dendrites and somata. Systematic modifications in patterns of differentiation of populations and individual thalamic axons and their projection neurons in the thalamus, granule cell dendrites, and neuropil compartments within barrel subdivisions will be compared in each instance to barrel field after neonatal ablation of the homeomorphic mystacial vibrissae, an intervention known to disrupt the differentiation of the barrel cell pattern during a critical period early in postnatal development. Such modifications are the key to testing hypotheses of the sequence of normal cellular events of identified axon-dendrite interactions in the CNS that are dependent upon, and presumably determined in part by, influences ascending to the cortex via the thalamus as transmitted from the brainstem and peripheral receptors. Understanding these principles of cortical development elucidated in this model system will assist in defining the structural basis of certain neurological developmental disabilities including mental retardation that may involve developmental defects in fundamental axonal-dendritic interactions that establish functional and structural neuronal assemblies.
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