Alteration of neuronal synaptic complement during regeneration and axonal sprouting of rat spinal cord

Spinal cord hemisection results in limited regeneration of nerve fibers and the sprouting of intact nerve fibers proximal to the site of lesion. Electron microscopically the nerve fibers form new synaptic complexes. The following study was undertaken in the rat to determine the synaptic profile of neurons during the regenerative process. The spinal cords of 40 rats were hemisected at vertebral segment T-2 and 5 animals per group (in addition to 5 normals) were utilized 10, 20, 30, 45, 60, and 90 days posthemisection. Tissue was prepared by the Rasmussen technique for the light microscopic demonstration of boutons. In addition, five animals had the cord hemisected and the spinal cord tissue was prepared for electron microscopy 40 days postoperatively. Bouton counts were made on perikaryon and primary dendrite (of the same neuron) of neurons in lamina IV, lamina VII, and on motoneurons. Statistical analysis of counts from coded material was carried out utilizing a polynomial regression, analysis of variance, and a Neuman-Keuls a posteriori analysis. The number of boutons on the perikaryon of neurons on the operated side demonstrated a significant decrease in boutons at 10–20 days postoperative followed by a significant increase in boutons at 30 days to levels below normal innervation. This reinnervation was followed by a significant secondary loss of boutons from 30 to 60 days. This trend of bouton alteration was repeated (with minor variations) on the perikaryon of neurons on the unoperated side of the spinal cord. This general trend was repeated on the primary dendrite on both operated and unoperated side of the spinal cord. However, the number of boutons on primary dendrite usually returned to normal. The regenerated boutons (30 days) frequently contained granular vesicles (predominantly 900 Å). The boutons that degenerated 30–60 days had all combinations of synaptic vesicles. This is an indication that former and new synaptic complexes were degenerating. The alteration of boutons on perikaryon and primary dendrite following hemisection suggests: that there is a critical period of initial denervation (0–20 days); that reinnervation occurs within the first 30 days; and that a secondary denervation occurs after 30–60 days. This recombination of neuronal circuits may represent an accelerated view of a dynamic continuum which imparts information to denervated neurons about altered neuronal circuitry adding a further dimension to the plasticity of the adult nervous system.