Among the forms of neuroplasticity that have been described in the injured spinal cord are axonal sprouting and regeneration into transplants of injured central nervous system. Both processes involve changes in afferent projections that are likely to modify receptor properties of postsynaptic cells and may be influenced by subsets of receptors present on the postsynaptic cells. The proposed research will examine neurotransmitter receptors in experimental models of spinal reactive reinnervation and regeneration in order to determine (1) the changes that occur on target neurons when afferent innervation changes and (2) whether receptors play a regulatory role in spinal reactive reinnervation and regeneration. The model of sprouting will be L1-S2 dorsal rhizotomy and the model of regeneration will be fetal spinal cord transplantation with dorsal root apposition. To examine changes that occur in postsynaptic cells, the first set of experiments will use receptor binding autoradiography for the predominant tachykinin and serotonin receptor subtypes in the dorsal horns (NK1 and 5HT1?) and for the NMDA receptor. In situ hybridization will also be used for NK1 and 5HT1? receptor mRNA's to identify specific cells in the dorsal horn. To examine the regulating role that receptors may play, the NMDA antagonist MK-801 will be used in the same models. Quantitative immunocytochemistry will be used to evaluate the effects of MK-801 on sprouting and regeneration. Receptor binding autoradiography will also be used to evaluate the effects of MK-801 on receptors. These experiments will help to understand the extent to which postsynaptic neurotransmitter receptors participate in and play a regulatory role in spinal sprouting and regeneration. The understanding may provide a further basis for rational treatments of spinal injury.
| Croul, S E; Flanders, A E (1997) Neuropathology of human spinal cord injury. Adv Neurol 72:317-23 |
| Croul, S; Sverstiuk, A; Radzievsky, A et al. (1995) Modulation of neurotransmitter receptors following unilateral L1-S2 deafferentation: NK1, NK3, NMDA, and 5HT1a receptor binding autoradiography. J Comp Neurol 361:633-44 |
