Enhancement of bistability in spinal motoneurons in vivo by the noradrenergic α1 agonist methoxamine

R. H. Lee, C. J. Heckman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


Like many types of motoneurons, spinal motoneurons in the adult mammal can exhibit bistable behavior. This means that short periods of excitatory input can initiate long periods of self-sustained firing and that equally short periods of inhibition can return the cell to the quiescent state. Usually, the presence of one of the monoamines (either serotonin or norepinephrine) is required for spinal motoneurons to express bistable behaviors. Because the decerebrate cat preparation has tonic activity in monoaminergic fibers that originate in the brain stem and project to spinal motoneurons, these cells sometimes exhibit bistable behavior. However, exogenous application of the noradrenergic α1 agonist methoxamine greatly enhances bistable behavior in the decerebrate. The goal of this study was to identify the mechanisms of this action of methoxamine. The total persistent inward current (I(PIC)) in spinal motoneurons in the decerebrate cat was measured from I-V functions generated by triangular voltage commands applied using discontinuous single electrode voltage clamp. The effect of methoxamine on I(PIC) was assessed by comparing its properties in a control cell sample without methoxamine to its properties in a sample of cells obtained after application of methoxamine. In most experiments, at least one celt was obtained from each sample. Our results showed that methoxamine approximately doubled the amplitude of I(PIC) without changing its onset voltage, its offset voltage, or its persistence. The reduced amplitude was a consistent finding within experiments and so was unlikely to be caused by interanimal variability. In addition, methoxamine depolarized motoneurons without altering their input conductances, so that a smaller amount of current was required to reach the onset voltage of I(PIC). These effects of methoxamine were approximately equal in all cells. As a result of these changes, methoxamine greatly enhanced the tendency for motoneurons to become bistable. It is proposed that the methoxamine-induced increase in the amplitude of I(PIC) is effective in enhancing the duration of bistable firing because this increase makes I(PIC) more resistant to the deactivating effects of the afterhyperpolarizations between spikes.

Original languageEnglish (US)
Pages (from-to)2164-2174
Number of pages11
JournalJournal of neurophysiology
Issue number5
StatePublished - 1999

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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