""""""""Degenerative"""""""" neurologic diseases in which neurons die without know cause raise the question of how nerve cells are normally maintained throughout life. Trophic relationships of neurons with other neurons and peripheral targets are known to be important for neuronal survival during development and normal function in maturity. This proposal is designed to study trophic influences on the morphology and survival of mammalian neurons. The proposal is divided into two parts. Part 1 will explore the trophic regulation of dendritic arbors by target interactions. These experiments will be done in autonomic ganglia utilizing intracellular staining with horseradish peroxidase. Three types of experiments will be carried out: 1) The effects of target interactions on dendritic arbors in adult animals will be assessed during target deprivation by axotomy and after reinnervation. 2) The role of target interactions in regulating dendritic development will be studied by increasing or decreasing the amount of target tissue innervated by developing autonomic ganglion cells. 3) Finally the effects of a known target-derived molecule (nerve growth factor) on the developing dendritic arbors of sympathetic ganglion cells will be explored. The goal of these studies is to elucidate factors which determine the dendritic complexity of mammalian neurons. Part 2 will investigate the influence of trophic interactions on neuronal survival. Two types of experiments will be done: 1) will determine the extent of naturally occurring cell death in autonomic ganglia of young and aged adult animals and explore afferent and efferent influences on cell survival. These experiments will utilize new imaging techniques which allow repeated observations of individual living neurons in vivo. 2) will extend these studies of trophic influences on neuronal survival to mammalian motor neurons with a focus on whether neurons in different motor pools differ with respect to their target dependencies. Work in this section is directed at the idea that a deficiency of trophic support may be involved in the pathogenesis of a specific neurodengenerative disease, amyotrophic lateral sclerosis.
| Ruit, K G; Snider, W D (1991) Administration or deprivation of nerve growth factor during development permanently alters neuronal geometry. J Comp Neurol 314:106-13 |
| Snider, W D; Palavali, V (1990) Early axon and dendritic outgrowth of spinal accessory motor neurons studied with DiI in fixed tissues. J Comp Neurol 297:227-38 |
