NEUROTROPHIN ACTIONS ON V PRIMARY AFFERENT DEVELOPMENT

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Proposed studies will test the general hypothesis that whisker-related pattern formation occurs as a direct result of neurotrophically regulated, naturally occurring cell death in the t rigeminal (V) ganglion. Anatomical and electrophysiological methods will be used in conjunction with various fetal neurotrophin augmentation regimens to determine mechanisms responsible for neurotrophin-induced failed pattern formation in V primary afferent neurons. Three Specific Aims are; 1) As the initial step in characterizing the role of neurotrophin-4/5 NNT- 4/5 in the development of the V system, V primary afferent projections will be studied after supplementating NT-4/5 levels in fetal rats. 2) To determine whether nerve growth factor (NGF) and NT-4/5 impact on the survival of selective populations of fetal ganglion cells, these two neurotropins will be augmented in fetal rats. At varying intervals, V ganglia will be processed immunohistochemically for markers of specific types of gangglion cells. 3) To assess whether the actions of NGF and NT-4/5 on central V patterns are due to altered peripheral projections (neurotropic effects), the innervation of the whiskerpad will be studied in neurotrophically manipulated arats using intra-axonal labeling, retrograde double-labeling, signle unit recording, electron microscopic, and immunohistochemical axon staining methods. These experiments are most efficiently carried out in this Program Project because of the expertise, baseline data, and materials made available by Drs/ Andrade, Bennett-Clarke, Golden, Jacquin, Johnson, Rhooades, Rice, Woolsey and Zahm. CORE "morphometry" and "EM" facilities will also be used extensively. Neurotrophins and assays will be provided by Dr. E.M. Johnson and Regeneron. Proposed experiments may implicate general principles suiding somatosensory development in humans because of recent indications that humans have somatotopically parcellated, barrel-like aggregations in nucleus principalis and the dorsal column nuclei (Noriega and Wall '91). In addition, biological actions of neurotrophic factors will revealed that may be of future use in treating certain neuropathic disorders