This project is concerned with the effects of injury on the early development and differentiation of spinal motoneurons in the bullfrog tadpole. The long-term goal is to understand the mechanisms whereby developmental processes may ameliorate the consequences of damage to the nervous system. Studies such as those proposed here are not feasible in mammals because of the fragility and inaccessibility of the fetus in utero. The relatively large size of the bullfrog tadpole, even at the initial stages of motoneuron birth and differentiation, will allow the effects of axotomy on motoneuron maturation and on regulation of motoneuron number to studied in detail. The specific areas to be investigated include examining the role of the target in development, comparing effects of disconnection from the target versus axonal injury in development, and determining the conditions for motoneuronal survival following axotomy. These studies will involve quantitative light microscopy and electrophysiological recordings. A particular advantage of the bullfrog tadpole for these studies is that the isolated nervous system exhibits rhythmic discharges which, in the intact animal, underlie locomotion. A major focus of the electrophysiological studies will be to examine the effects of injury and disconnection from the target on the development of locomotor circuitry in the spinal cord, In addition, the effects of axotomy on the development and maintenance of monosynaptic inputs to the injured motoneurons will be determined.
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