One of the devastating effects of spinal cord injury (SCI) is the atrophy of musculature supplied by neurons that are located caudal to the lesion site. The affected muscles not only exhibit a reduction in size, but the fibers that remain often display alterations in functional properties. It is well known that patterns of motoneuronal activity can dictate the phenotype of the muscle fibers they supply. In this regard, some alleviation of the muscular symptoms of SCI has been produced by two different techniques. One approach involves a passive exercise training regimen, which at least partially reverses the functional alteration. The other approach involves grafting fetal spinal cord implants (FSCI) into the site of the lesion. This procedure has also been shown to partially alleviate muscle atrophy, presumably by inducing the motoneurons in close proximity to the FSCI to drive muscle contraction in a pattern that maintains muscle structure and function. The motoneuronal properties and spinal cord circuitry that are essential for the maintenance of appropriate muscle structure and function after SCI have not been well defined. The major goal of this series of experiments is to describe these physiological and anatomical properties of the spinal cord environment. We will use intracellular and extracellular electrophysiological recording from spinal cord slice and whole spinal cord preparations to study motoneuronal function. To determine the anatomical correlates of these physiological studies, we will label individually identified motoneurons by intracellular injection and describe the synaptic inputs to motoneurons with immunocytochemical techniques. We will perform these analyses during three periods of time in which changes in motoneuronal firing pattern are known to influence the functional integrity of muscle: 1.) the critical developmental time point when the activity pattern of motoneurons is first able to influence muscle fiber phenotype, 2.) the time following SCI in a juvenile rat or embryonic chick in which alterations in motoneuronal activity caudal to the lesion result in loss of function and muscle atrophy, 3.) the period of time in which SCI in a juvenile rat is followed by a graft of fetal spinal cord, a situation in which muscle atrophy is reduced presumably due to the graft inducing the adjacent motoneurons to support their peripheral target muscles. We will use both the postnatal rat and embryonic chick preparations. The rat and chick models provide well developed preparations to study SCI. By using a comparative approach we will combine the strengths of both model systems to identify common, important electrophysiological and morphological properties of motoneurons that are necessary for the maintenance of the muscles supplied by these neurons. Understanding the functional, cellular and pharmacological phenomena that influence patterns of motoneuronal electrical activity is essential for designing successful transplantation and pharmacological strategies for intervention and rehabilitation following SCI.
