Electrophysiological effects of 4-aminopyridine on fictive locomotor activity of the rat spinal cord in vitro

Abstract

Recently the K+ channel blocker 4-aminopyridine (4-AP) has been suggested to be useful to improve motor deficits due to spinal cord lesions. There is, however, little basic research support for this action of 4-AP. In this study we have used as a model the neonatal mammalian spinal cord in vitro that generates a rhythmic activity termed fictive locomotion (induced by bath-application of NMDA + 5-HT) with phasic electrical discharges alternating between flexor and extensor motor pools and between left and right motoneurons within the same segment. When 4-AP was added in the presence of sub-threshold concentrations of NMDA + 5-HT, there was facilitation of fictive locomotion which appeared with alternating patterns on all recorded ventral roots (VR). Furthermore, in the presence of 4-AP, weak dorsal root (DR) stimuli, previously insufficient to activate locomotor patterns, generated alternating discharges from various VRs. The present data show that 4-AP could strongly facilitate the locomotor program initiated by neurochemicals or electrical stimuli, indicating that the spinal locomotor network is a very sensitive target for the action of 4-AP. © 2005 Springer-Verlag.