Influence of proximal axonal swellings on rhythmic motoneuron firing

Previous studies of electrophysiological function of motoneurons (MNs) in animals with beta, beta'-iminodipropionitrile (IDPN) neuropathy revealed alterations in action potential discharge indicative of enhanced MN excitability. These changes, particularly manifested in increased numbers of delayed depolarizations and repetitive firing upon single stimulation, are strikingly similar to those observed in axotomized MNs. The present study extends the parallels between axotomized and neuropathic conditions by assessing rhythmic firing responses of MNs to direct current injection in cats treated with IDPN (50 mg/kg/week for 5 weeks). Changes in excitability and frequency-current relationships were studied on Day 35 of IDPN intoxication and compared to those reported for axotomized (chromatolytic) MNs. In treated animals, lumbar MNs had increased thresholds for sustained discharge, tended to achieve higher maximum discharge frequencies, and adapted less to continuous current injection. In untreated cats 74% of MNs exhibited firing in both primary and secondary ranges, whereas only 39% of those in treated animals made the transition to secondary range firing. Most fired monotonically in the primary range with unchanged slope of the frequency-current relationships. When achieved, secondary range slopes were one-third of normal. MN afterhyperpolarization peak amplitude, duration, and conductance were reduced while input resistance was increased. The findings are discussed in terms of altered MN and dendritic excitability induced by the neuropathy, and similarities to electrophysiological changes in axotomized MNs.