Intraspinal stimulation caudal to spinal cord transections in rats

Many laboratories have reported the successful regeneration of neurons across damaged portions of the spinal cord. Associated improvements in hindlimb locomotor movements have been attributed to the formation of functional neuronal connections with the locomotor central pattern generator (CPG). But regenerating axons generally extend no more than 10mm caudal to the lesion sites, terminating about 20mm short of the lumbar segments thought to contain the CPG. It has therefore tacitly been assumed that the locomotor improvements were due to activation of propriospinal neurons relaying excitation to the CPG. Here we report a test of this assumption, which we call the propriospinal hypothesis. Intraspinal microstimulation (ISMS) was used to activate the putative propriospinal relay neurons. Approximately 2-3 weeks after complete spinal cord transection at T8-T9 in rats, an array of 6 Pt-Ir microwires was chronically implanted in the intermediate and ventral grey matter of T10-T12 segments. ISMS pulse trains with amplitudes of 0.8-0.9 times threshold for activating axial muscles were delivered during open field locomotor tests (BBB). ISMS significantly increased BBB scores over control tests, but did not produce limb coordination and weight-bearing sufficient for locomotion. These results support the main assumption of the propriospinal hypothesis, namely that neuronal activity elicited in thoracic spinal segments caudal to a complete spinal cord transection may propagate caudally and activate the locomotor CPG. Supported by CIHR. Page 2 of 22