Ongoing collaborations between neuroscientists at the St. Louis University School of Medicine, Medical College of Ohio, Henry Ford Foundation, University of Iowa, and Washington University School of medicine will continue to address mechanisms responsible for normal developmenta nd injury-induced reorganization in mammalian sensory systems. The central trigeminal (V) representations of the rodent whiskers (barrels) are being used as a model. Seven projects will test hypotheses pertaining to: 1) What makes whisker-related patterns? 2) What maintains whisker-related patterns? 3) What determines orderly axon target selectiona nd ingrowth patterns? 4) What determines orderly development of dendritic trees? 5) How do """"""""modulatory"""""""" pathways develop and impact on the barrel neuraxis? A CORE provides morphometry, electron microscopy, tissue culture, animal and administrative facilities, and ensures timely communication between projects and external review. The 1st project will use organotypic tissue culture a d tract tracing methods to uncover mechanisms of primary afferent target selection and ingrowth. The next project will use anatomical labeling, infraorbital nerve injury and axoplasmic transport blocking methods to reveal mechanisms responsible for potnatal pattern maintenance in the V brainstem complex. The next project will test the hypothesis that whisker-related pattern formation occurs as a direct result of neurotrophically regulated, naturally occurring cell death in the V ganglion. Anatomical and electrophysiological methods will be used after various fetl neurotrophin augmentation regimens to determine mechanisms responsible for neurotrophin-induced changes in V primary afferent projection pattrns. The next project focusses on the normal development of, and actions of neurotrophins upon, cells in V nucleus principalis. The next project will use anatomical and electrophysiological methods to examine the development of thalamocortical neurons and the role of specified afferents and target factors in axodendritic arborization. The next project will test the hypothesis that serotonin influences thalamocortical development by acting at 5HT ib receptors located on the terminals of thalamic axons to presynaptically inhibit thalamocortical synaptic transmission; this action modulates activity-dependent process involved in the development of terminal arbors. The last project offers anatomical and pharamcological experiments to assess the normal development, specificity and activity-related plasticity of the somatosensory cortical projections to the thalamus adnd V brainstem complex. These studies will reveal general principles guiding somatosensory development in humans because humans also have somatotopically parcellated, barrel-like aggregations in the V brainstem nucleus. We will also provide new information ont he biological actions of neurotrophic factors that may be of future use in treating certain neuropathic disorders.
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