This research is devoted to the development of the corticothalamic system joining the somatosensory area of the cerebral cortex to the ventral posterior nucleus of the thalamus. Corticothalamic fibers far outnumber those of the thalamo-cortical projection, and provide the main pathway for integrating the activities of the cerebral cortex and thalamus in relation to the state of consciousness. However, their developmental history and especially their potential role in organizing the development of the body-specific representation in the thalamocortical projection during the perinatal period has not been examined. The research proposed will examine the growth of individual corticothalamic fibers as they establish their patterns of distribution in the thalamus, during the period when the cortex is itself being innervated by the thalamus. The principle experimental model is a mouse in vitro preparation. Labeling of populations of growing axons will be carried out to establish temporal patterns of innervation and labeling of single axons and their parent cells by intracellular injections of dyes will establish the morphogenetic sequence of cell-type specific projections. The influence of specific growth factors on corticothalamic cell and axon growth will be examined. Physiological methods involving whole cell recording, in vitro, will measure the maturation of corticothalamic function and its interactions with sensory inputs from the skin via various forms of receptors. The synapses and their associated receptors will be identified and quantified using electron microscopic immunocytochemistry. The overall hypothesis is that interactions between corticothalamic fibers and thalamic cells are critical in establishing the fine grain topography that characterizes thalamocortical innervation. This forms a substrate for interactions between thalamus and cortex that underlie changes in conscious state in maturity. It is proposed that developmentally regulated changes in synaptic distribution and the receptors engaged are critical to the normal maturation of these interactions. Defective maturation may be a concomitant of or a basis for certain forms of seizures in young individuals.
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