Title: Dopaminergic Modulation of Locomotor Network Activity in the Neonatal Mouse Spinal Running Title: Dopaminergic Modulation of Locomotion Introduction

19 20 Dopamine is now well established as a modulator of locomotor rhythms in a variety of 21 developing and adult vertebrates. However, in mice while all five dopamine receptor subtypes 22 are present in the spinal cord it is unclear which receptor-subtypes modulate the rhythm. 23 Dopamine receptors can be grouped into two families – the D 1/5 receptor group and the D 2/3/4 24 group that have excitatory and inhibitory effects respectively. Our data suggest that dopamine 25 exerts contrasting dose-dependent modulatory effects via the two-receptor families. Our data 26 show that administration of dopamine at concentrations greater than 35 µM slowed and 27 increased the regularity of a locomotor rhythm evoked by bath application of 5-HT and NMA. 28 This effect was independent of the baseline frequency of the rhythm that was manipulated by 29 altering the NMA concentration. We next examined the contribution of the D 1 and D 2 receptor-30 like families on the rhythm. Our data suggest that the D 1-like receptor contributes to enhancing 31 the stability of the rhythm. Overall, the D 2-like family had a pronounced slowing effect on the 32 rhythm however, quinpirole, the D 2-like agonist, also enhanced rhythm stability. These data 33 indicate a receptor-dependent delegation of the modulatory effects of dopamine on the spinal 34 locomotor pattern generator.