The ultimate goal of spinal cord injury research is to achieve functional restitution. Spinal cord regeneration research is directed toward establishing functional restitution by the growth of new axon pathways through the damaged regions of the spinal cord. Another approach to functional recovery after spinal cord injury would be to activate already existing, functionally latent axon pathways found in the non-damaged regions of the spinal cord. Recently, several examples of functionally latent pathways have been demonstrated in many regions of the CNS. The pathways are latent because the synapses which connect them to neurons initialliy are functionally ineffective in firing the postsynaptic cell. Within hours after injury, however, the functionally ineffective synapses are converted to ones which become capable of activating the postsynaptic target neuron. In many instances the functional capabilities of the animal are markedly improved after synaptic conversion. Although the functional unmasking of ineffective synapses has been demonstrated physiologically in many regions of the CNS, the morphological basis for the synaptic conversion has not been discovered. For years, the P.I. has associated functionally ineffective synapses to the expression of a respiratory reflex in spinal cord injured rats. In this model, the conversion of the ineffective synapses to effective ones results in the functional recovery of a portion of the animal's diaphragm which had been paralyzed by spinal cord injury. Through an extensive EM analysis of the phrenic nucleus in normal and spinal cord injured rats, the P.I. has discovered specific morphological alterations of the normal phrenic nucleus ultrastructure occurring within hours after injury which he hypothesizes are related to the conversion of functionally ineffective synapses. Such alterations have never before been shown to occur so rapidly after spinal cord injury. The long-term objective of this research is to substantiate the relationship of these morphological alterations to the physiological conversion of functionally ineffective synapses.
The specific aims are: 1) to focus in on the specific consequences of spinal cord injury which induce the alterations and 2) to quantitate the alterations using computer morphometric analysis techniques. When this work is complete, it will provide new information showing that certain rapid changes can occur in the morphology of the spinal cord after injury and that there changes may be related to the functional recovery of paralyzed muscle.
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