Regenerated dorsal root fibers form functional synapses in embryonic spinal cord transplants

Abstract

1. The aim of the present study was to determine whether synapses formed by dorsal root afferents that regenerate into intraspinal transplants of fetal spinal cord are functional. Severed L4 or L5 dorsal root stumps were placed at the bottom of dorsal quadrant cavities made in the lumbar spinal cords of adult rats and juxtaposed to embryonic day 14 spinal cord transplants. 2. In animals examined 5-10 weeks later, we recorded extracellularly in transplants from 43 units that fired in response to electrical stimulation of the implanted dorsal root. Latency fluctuations of extracellular firing that increase with stimulus and failure to follow high-frequency and posttetanic potentiation of extracellular firing stimulation suggest that synapses with conventional properties are formed between regenerating afferents and transplant neurons. Limited intracellular recordings confirmed the existence of excitatory postsynaptic potentials in transplant neurons after dorsal root stimulation. 3. In 16 units, extracellular firing occurred in response to single shock stimulation. The remainder of the units required two or more dorsal root shocks to evoke firing; some of these connections also may be monosynaptic. 4. Under the assumption that single shock firing was most likely the result of monosynaptic connections between transplant neurons and regenerated dorsal root fibers, we estimated the conduction velocities of regenerated fibers. These estimates suggest that fibers with conduction velocities in the C, A delta, and A alpha/beta ranges regenerate into transplants of embryonic spinal cord. 5. The results demonstrate that regenerated dorsal root axons establish functional synaptic connections with transplant neurons. The implications for using fetal transplants to help rebuild spinal reflex circuits after spinal cord injury are considered.