The nervous system must cope with increasing body size as the juvenile matures to a full-grown adult. Without some form of compensation, sensory discrimination and motor precision would be degraded as the ratio of neurons to target size decreased. One solution to this problem is to add neurons. Using the bullfrog as an experimental model, the first objective is directed toward this fundamental question of neural organization: Are neurons added to the nervous system during adulthood? Our initial studies provide strong preliminary evidence that neurons are indeed added as a function of body size to both the central and peripheral nervous systems. Further aims for this objective include determining the mechanism whereby neurons are added and the relationship between neuron number and target size. The proposed experiments entail cell counts in frogs of different sizes, the use of antibodies directed against cellular markers characteristic of neurons of a particular type, and injection of 3H-thymidine to determine whether new neurons are being born during adulthood. To be of use, neurons that are added must innervate their proper targets, which in turn implies that mechanisms of axon guidance are still operating in the established nervous system. However, many neurons, such as spinal motoneurons in the bullfrog tadpole, are able to regenerate axons to their proper targets only if axotomy occurs early in development (Farel and Bemelmans, 1986; Farel and Wray, 1989). The second objective is directed toward understanding mechanisms of axon guidance during regeneration and the reasons for their failure to be expressed after early developmental stages. Attaining this objective is a first step toward understanding how axons of neurons that are added during adulthood are able to innervate their appropriate targets. These experiments entail assessing regenerative specificity by the use of retrogradely transported markers, explant cultures to test for diffusible tropic factors, and electron microscopy to monitor hindlimb development.
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