Interactions between neurons and between neurons and glial cells have been shown by a number of researchers to be critical for normal development of the nervous system. The proposed research is a study of developmental interactions among neurons and glial cells in the forming central nervous system of a moth, where much of development occurs postembryonically. Current work on the antennal system of the moth Manduca sexta suggests that, just as in vertebrates, sensory axons guide many aspects of the development of their targets, in this case, the antennal lobes of the brain. The goal of the proposed research is to understand at a cellular level the nature of the influence exerted by the antennal sensory axons. Previous work has indicated that the antennal axons influence the morphological organization of the neuropil, the disposition and morphology of glial cells, and the distribution of synapses in the antennal lobe. Several lines of evidence lead to the hypothesis that the glial cells of the lobe may be acting as intermediaries between sensory axons and second-order antennal-lobe neurons in some of these interactions. We propose to test this hypothesis using primarily two experimental models: antennal lobes that have been deprived of antennal axons throughout development, and antennal lobes in which the number of glial cells has been severely reduced through exposure to gamma-irradiation during critical stages of glial proliferation. The development of the characteristic glomeruli of the lobe, the distribution and numbers of synapses in the lobe, and the development of the branching patterns of individual antennal-lobe neurons will be monitored and compared with normal. If glial-deficient lobes resemble uninnervated lobes in any of these parameters (as preliminary experiments indicate they may), this will be interpreted as evidence that glial cells were a necessary conduit for flow of insstructive information from sensory axons to antennal-lobe neurons. Parameters that do depend upon the presence of sensory axons but not upon the presence of glia will be interpreted as resulting most likely from direct neuron-neuron interactions.
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