Proposed studies will test the general hypothesis that whisker-related patterns (barrels) form in the brainstem, ahalamus and cerebral cortex as a direct consequence of spatiotemporally patterned, naturally occur=ring cell death in the trigeminal nucleus principalis that is regulated by the actions of neurotrophins on trigeminal ganglion cells. Anatomical, electrophysiological and morphometric methods will be applied to normal postnatal rats or postnatal rats that have received supplemental, exogenous nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and/or neurotrophin-3 (NT-3) during fetal intervals to answer the following questions: 1) Does the timecourse of naturally occuring cell death in nucleus principalis predict the timecourse of whisker-related pattern formation in nucleus principalis? 2) Are whisker-related patches in principalis produced by a patterned distribution of principalis cells and terminals that undergo naturally occurring apoptosis-like degeneration, therein producing inter-patch septae? 3) Does chronic augmentation of NGF, BDNF and /or NT-3 levels ameliorate naturally occurring cell death and affect pattern formation in principalis cells? 4) Under conditions that minimize principalis cell dath, do principalis cells develop normal dendritic trees; is the nucleus somatotopically organized; and is there a disproportionate number of cells with receptive fields on interwhisker surfaces? 5) Uner conditions that minimize principalis cell death, do principalis cells develop normal thalamic projections and do barrels develop in the cerebral cortex: These experiments therefore focus on the normal development of, and actions of neurotrophins upon, principalis cells, their thalamic projections and cortical representations. Studies addressing the normal development of, and actions of neurotrophins upon, trigeminal ganglion cells form a necessary foundation for this research and these experiments will be done in collaboration with other Program Project members (Drs. Andratde, Arends, Bennett-Clarke, Chiaia, Golden, Henderson, Johnson, Rhoades, Snider, Woolsey and Zahm). CORE """"""""morphometry"""""""" and EM facilities will be employed. Neurotrophisn and their assays will be provided by Dr. E.M. Johnson and Regeneron. Proposed experiments may implicate general principles guiding somatosensory development in humans because of recent indications that humans have somatotopically parcellated, barrel-like aggregations in nucleus pri cipalis and the dorsal column nuclei (Noriega and Wall '91). In addition, biological actions of neurotrophic factors will be revealed that may be of future use in treating certain neuropathic disorders.
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