Alterations of action potentials and the localization of Nav 1 . 6 sodium channels in spared 1 axons after hemisection injury of the spinal cord in adult rats . 2 3

25 Previously we reported a pronounced reduction in transmission through surviving axons 26 contralateral to chronic hemisection (HX) of adult rat spinal cord. To examine the cellular 27 and molecular mechanisms responsible for this diminished transmission, we recorded 28 intracellularly from lumbar lateral white matter axons in deeply anesthetized adult rats in 29 vivo and measured the propagation of action potentials (APs) through 30 rubrospinal/reticulospinal (RST/RtST) tract axons contralateral to chronic HX at T10. We 31 found decreased excitability in these axons, manifested by an increased rheobase to 32 trigger APs and longer latency for AP propagation passing the injury level, without 33 significant differences in axonal resting membrane potential and input resistance. These 34 electrophysiological changes were associated with altered spatial localization of Nav1.6 35 sodium channels along axons: a subset of axons contralateral to the injury exhibited a 36 diffuse localization (>10 μm spread) of Nav1.6 channels, a pattern characteristic of 37 demyelinated axons (Craner et al. 2004b). This result was substantiated by ultastructural 38 changes seen with electronmicroscopy, in which an increased number of large caliber, 39 demyelinated RST axons was found contralateral to the chronic HX. Therefore, an 40 increased rheobase, pathological changes in the distribution of Nav1.6 Na-channels, and 41 the demyelination of contralateral RST axons is likely responsible for their decreased 42 conduction chronically after HX and thus may provide novel targets for strategies to 43 improve function following incomplete spinal cord injury. 44 45 46