Sensory and motor function recover steadily from 1 to 4 weeks and then stabilizes in spinal-injured animals. The physiological and morphological factors underlying this recovery are not well understood. We have found a surprisingly poor correlations between morphologically defined damage at the lesion site and functional outcome. This suggests that factors besides the numbers axons crossing the lesion site play role in determining functional outcome. These factors include (i) physiological variables governing axonal conduction; (ii) axonal sprouting; and (iii) changes in excitability of secondary relay neurons. We propose to test the hypothesis that functional outcome depends on morphological changes at the synaptic level rostral and proximal to the lesion site. To test this hypothesis, we will ascertain whether the number of degenerating synaptic boutons in the lumbar cord and dorsal column nuclei at 6 days after injury correlates with functional impairments of axonal conduction and reflex excitability will be studied in rats after graded spinal cord contusions. Neuronal excitability will be examined by measuring relative latencies and amplitudes of evoked responses at peripheral, segmental (above and below the lesion), and supraspinal sites in response to peripheral and/or supraspinal activation. In a similar set of experiments, animals will be tested up to 3 months after injury and then all surviving axons in the lesion site will be transected. This experiment will test the hypothesis that the number of synaptic boutons arising from those axons, as indicated by the intensity of their degeneration, is proportional to the degree of sensory and motor recovery up to 3 months. A further set of experiments will address recovery and enhancement of function in greater physiological detail. Axonal conduction and neuronal excitability will be examined up to 1 months after graded, contusions, and invasive spinal cord recordings will be used to monitor neuronal responsiveness to peripheral and supraspinal inputs. We will test whether the normal time course of recovery after injury is mediated by improvement in axonal conduction, by an increase in neuronal excitability (facilitation or disinhibition), or both. In the process, we will also investigate the ability of peripheral stimuli and 4-AP to enhance segmental responses to descending activation. In particular, we will determine whether the enhancement produced by 4-AP is due to improvement of axonal conduction or to increased segmental or supraspinal excitability.
