The long-term objective of this research is to determine the mechanisms that underlie recovery and alteration of function following partial denervation of the adult mammalian central nervous system. Previous work on this project has led to new hypotheses to explain the immediate and long term physiological changes observed in spinal cord dorsal horn cells following interruption of descending pathways. It is proposed that the immediate decline in responsiveness to peripheral stimuli (""""""""spinal shock"""""""") is due to a loss of descending inhibition acting on interneurons that mediate presynaptic inhibition of afferent activity. It is postulated that the long term recovery of responsiveness to peripheral inputs and eventual return of spontaneous activity to normal levels are due to the development of denervation supersensitivity. The proposed experiments are designed to test these hypotheses and the alternative, more conventional hypotheses that spinal shock is due to mechanisms related to acute injury per se, and that long-term increases in responsiveness to peripheral stimuli are due to release of descending inhibition. To test whether spinal shock is due to injury per se, the applicant plans to measure dorsal horn cell responsiveness to peripheral stimuli following acute dorsolateral funiculus lesions and compare this with responsiveness under acute blockade of the DLF by lidocaine microinjection. To test whether dorsal horn cells are under tonic descending postsynaptic inhibition, intracellular methods will be used to measure their membrane potentials before and after lidocaine blockade of the DLF. To test whether primary afferent fibers are under tonic presynaptic inhibition, dorsal root potentials and microstimulation thresholds of primary afferent terminals will be measured before and after lidocaine blockade. To test for the development of denervation supersensitivity. The effects of microinjecting serotonin and peptide neurotransmitters on the response properties of dorsal horn neurons will be evaluated in normal and DLF lesion animals at survival times from < 1 to 60 days. These studies are relevant to our understanding of the physiological consequences of central nervous system injury, and of the ability of the nervous system to adapt to such injury.
