PROPERTIES OF CENTRAL AXONS AT PERIPHERAL TARGETS

现在已经确定，虽然中枢神经纤维会

It is now well established that although central nerve fibers will not elongate over long distances within the adult mammalian central nervous system (CNS), they readily do so within the peripheral environment of nerves inserted into the CNS. Despite the variety of neurons with this property, there has so far been no report of whether the regenerating axons are induced by their peripheral environment and target organs to develop terminal specializations capable of sensory or motor transduction. If such receptors are formed, then peripheral nerve grafts may be of value in restoring function to limbs rendered paralysed and numb by spinal cord injury. Significantly, our preliminary experiments have established that effective synapses are formed on denervated skeletal muscle by central fibers regenerating along ventral roots replanted into the lateral column. Central nerve fibers will be led from the spinal cord via replanted ventral and dorsal roots to reinnervate either denervated skeletal muscle or denervated skin. The ventral and dorsal roots will be replanted into the ventro-lateral and dorso-lateral columns respectively, either near to their normal junction or, via a graft, to a site above the supposed location of an injury to the spinal cord. After 4-8 months the rats will be assessed physiologically and histologically to determine a) whether motor or sensory terminals have formed, b) the identities of the fibers involved, and c) whether the regenerating neurons contribute to useful motor or sensory function. Successful motor reinnervation will be assessed, in part by determining the presence of contractions of the appropriate muscles upon direct stimulation of the replanted ventral root, and upon indirect (synaptic) activation of motoneurons. The return of muscle reinnervation will also be monitored serially using EMG recordings. Successful sensory reinnervation will be determined, in part, by mapping the sensory fields of individual fibers teased from the replanted roots, and by determining the presence of central responses evoked by sensory stimulation. Another experiment will examine whether axonal damage is a prerequisite to neurite production.