Dopaminergic modulation of locomotor network activity in the neonatal mouse spinal cord

Abstract

Sharples SA, Humphreys JM, Jensen AM, Dhoopar S, Delaloye N, Clemens S, Whelan PJ. Dopaminergic modulation of locomotor network activity in the neonatal mouse spinal cord. J Neurophysiol 113: 2500 -2510, 2015. First published February 4, 2015 doi:10.1152/jn.00849.2014.-Dopamine is now well established as a modulator of locomotor rhythms in a variety of developing and adult vertebrates. However, in mice, while all five dopamine receptor subtypes are present in the spinal cord, it is unclear which receptor subtypes modulate the rhythm. Dopamine receptors can be grouped into two families-the D 1/5 receptor group and the D 2/3/4 group, which have excitatory and inhibitory effects, respectively. Our data suggest that dopamine exerts contrasting dose-dependent modulatory effects via the two receptor families. Our data show that administration of dopamine at concentrations Ͼ35 M slowed and increased the regularity of a locomotor rhythm evoked by bath application of 5-hydroxytryptamine (5-HT) and N-methyl-D(L)-aspartic acid (NMA).This effect was independent of the baseline frequency of the rhythm that was manipulated by altering the NMA concentration. We next examined the contribution of the D 1 -and D 2 -like receptor families on the rhythm. Our data suggest that the D 1 -like receptor contributes to enhancement of the stability of the rhythm. Overall, the D 2 -like family had a pronounced slowing effect on the rhythm; however, quinpirole, the D 2 -like agonist, also enhanced rhythm stability. These data indicate a receptor-dependent delegation of the modulatory effects of dopamine on the spinal locomotor pattern generator. dopamine; locomotion; monoamine; spinal cord NEURAL CIRCUITS that produce basic rhythmic motor patterns of locomotion, in vertebrates, reside primarily in the spinal cord and are subject to neuromodulation from a wide range of sources both intrinsic and extrinsic to the spinal cord (Dunbar et al.

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“…; Sharples et al . ). Likewise, the difference in magnitude of the effect of these two drugs was much greater with respect to D1DR than D2DR, as well as DAT in vitro (Fig.…”

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