Potentiation of active locomotor state by spinal-projecting serotonergic neurons

Animals produce diverse motor actions that enable expression of context-appropriate behaviors. Neuromodulators facilitate behavioral flexibility by altering the output of neural circuits. Discrete populations of serotonergic (5-HT) neurons target circuits in the brainstem and spinal cord, but their roles in motor behavior are unclear. Here, we define the pre- and post-synaptic organization of spinal-projecting serotonergic neurons in mice and identify a role in locomotor control. While forebrain-targeting 5-HT neurons decrease their activity during locomotion, spinal-projecting neurons increase their activity in a context-dependent manner. Optogenetic activation of ventrally projecting 5-HT neurons does not initiate movement, but rather enhances the speed and duration of ongoing locomotion. Serotonergic neurons can influence motor output beyond periods of increased activity, indicating that neuromodulators can act over extended timescales. These findings indicate that the descending serotonergic system potentiates locomotor output and demonstrate a role for serotonergic neurons in modulating the temporal dynamics of motor circuits.