Functional connections are established in the deafferented rat spinal cordby peripherally transplanted human embryonic sensory neurons

Functionally useful repair of the mature spinal cord following injury requi res axon growth and the re-establishment of specific synaptic connections. We have shown previously that axons from peripherally grafted human embryon ic dorsal root ganglion cells grow for long distances in adult host rat dor sal roots, traverse the interface between the peripheral and central nervou s system, and enter the spinal cord to arborize in the dorsal horn. Here we show that these transplants mediate synaptic activity in the host spinal c ord. Dorsal root ganglia from human embryonic donors were transplanted in p lace of native adult rat ganglia. Two to three months after transplantation the recipient rats were examined anatomically and physiologically. Human f ibres labelled with a human-specific axon marker were distributed in superf icial as well as deep laminae of the recipient rat spinal cord. About 36% o f the grafted neurons were double labelled following injections of the fluo rescent tracers MiniRuby into the sciatic and Fluoro-Gold into the lower lu mbar spinal cord, indicating that some of the grafted neurons had grown pro cesses into the spinal cord as well as towards the denervated peripheral ta rgets. Electrophysiological recordings demonstrated that the transplanted h uman dorsal roots conducted impulses that evoked postsynaptic activity in d orsal horn neurons and polysynaptic reflexes in ipsilateral ventral roots. The time course of the synaptic activation indicated that the human fibres were non-myelinated or thinly myelinated. Our findings show that growing hu man sensory nerve fibres which enter the adult deafferentated rat spinal co rd become anatomically and physiologically integrated into functional spina l circuits.