Although the unmasking of functionally ineffective synapses has been demonstrated physiologically throughout the CNS, the morphological basis for the synaptic conversion has not been elucidated. In previous work, the P.I. associated functionally ineffective synapses with the delayed expression of the crossed phrenic phenomenon (CPP) in spinal cord injured rats and guinea pigs. IN this spinal cord injury model, the conversion of ineffective to effective synapses results in the functional recovery of 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. discovered specific morphological alterations of the normal phrenic nucleus synaptology which may be correlated with the physiological conversion of functionally ineffective synapses. The overall objective of this application is to carry out correlative quantitative physiological and morphological analyses to either prove or disprove causality between the above morphological and physiological events.
Five specific aims will test the following hypotheses: 1) that if injury-induced structural alterations in the phrenic nucleus are related to the unmasking of ineffective synapses, then there should be a temporal relationship between an increase in the alterations and an increase in diaphragm functional recovery, 2) that difference detected in the normal morphology of the rat phrenic nucleus during aging may be related to differences in the expression of the CPP immediately after spinal hemisection in young as compared to older adult rats, 3) that the spinal cord circuitry which enables older rats to moro fully express the CPP immediately after hemisection as compared to young adult animals is resistant to trauma, 4) that modifications of the phrenic morphological alterations should result in modifications of the expression of the CPP, and 5) that single phrenic motor axon recording techniques can be used to answer specific questions related to the firing patterns of phrenic neurons during the CPP as well as the specificity of motoneuron plasticity after spinal cord injury in general. The significance of the proposed research is that it may show that there is a detectable morphological substrate in the injured spinal cord that can be related to the functional recovery of muscle paralyzed by spinal cord injury.
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