Monoaminergic Control of Cauda-Equina-Evoked Locomotion in the Neonatal Mouse Spinal Cord

Abstract

Monoaminergic projections are among the first supraspinal inputs to innervate spinal networks. Little is known regarding the role of monoamines in modulating ongoing locomotor patterns evoked by endogenous release of neurotransmitter. Here we activate a locomotor-like rhythm by electrical stimulation of afferents and then test the modulatory effects of monoamines on the frequency, pattern, and quality of the rhythm. Stimulation of the cauda equina induced a rhythm consisting of left-right and ipsilateral alternation indicative of locomotor-like activity. First, we examined the effects of noradrenaline (NA), serotonin (5-HT), or dopamine (DA) at dose levels that did not elicit locomotor activity. Bath application of NA and DA resulted in a depression of the cauda-equina-evoked rhythm. Conversely, bath-applied 5-HT increased both the amplitude and cycle period of the evoked rhythm, an effect that was mimicked by the addition of 5-HT(2) agonists to the bath. Application of 5-HT(7) agonists disrupted the evoked rhythmic behavior. Next, we examined the effects of NA alpha(1) and alpha(2) agonists and found that the suppressive effects of NA on the rhythm could be reproduced by adding the alpha(2) agonist, clonidine, to the bath. In contrast, bath applying the alpha(1) agonist, phenylephrine, increased the amplitude and duration of the cycle period. Finally, the suppressive effects of DA were not replicated by the administration of D(1), D(2), or D(3) agonists although application of NA alpha(2) antagonists reversed the effects of DA. Application of D(1) agonists, increased the amplitude of the bursts but did not affect the cycle period. Our results indicate that monoamines can control the expression, pattern, and timing of cauda-equina-evoked locomotor patterns in developing mice.