Control of locomotion relies on motor loops conveying modulatory signals between brainstem and spinal motor circuits. We investigated the steering control of the brainstem reticular formation over the spinal locomotor networks using isolated brainstem-spinal cord preparations of male and female neonatal rats. First, we performed patch-clamp recordings of identified reticulospinal cells during episodes of fictive locomotion. This revealed that a spinal ascending phasic modulation of reticulospinal cell activity is already present at birth. Half of the cells exhibited tonic firing during locomotion, while the other half emitted phasic discharges of action potentials phase locked to ongoing activity. We next showed that mimicking the phasic activity of reticulospinal neurons by applying patterned electrical stimulation bilaterally at the ventral caudal medulla level triggered fictive locomotion efficiently. Moreover, the brainstem stimuli-induced locomotor rhythm was entrained in a one-to-one coupling over a range of cycle periods (2-6 s). Additionally, we induced turning like motor outputs by either increasing or decreasing the relative duration of the stimulation trains on one side of the brainstem compared to the other. The ability of the patterned descending command to control the locomotor output depended on the functional integrity of ventral reticulospinal pathways and the involvement of local spinal central pattern generator circuitry. Altogether, this study provides a mechanism by which brainstem reticulospinal neurons relay steering and speed commands to the spinal locomotor networks. Locomotor function allows the survival of most animal species while sustaining the expression of fundamental behaviors. Locomotor activities adapt from moment to moment to behavioral and environmental changes. We show that the brainstem can control the spinal locomotor network outputs through phasic descending commands that alternate bilaterally. Manipulating the periodicity and/or the relative durations of the left and right descending commands at the brainstem level is efficient to set the locomotor speed and sustain directional changes.
Descending neuromodulators from the brainstem play a major role in the development and regulation of spinal sensorimotor functions. Here, the contribution of serotonergic signaling in the lumbar spinal cord was investigated in the context of the generation of locomotor activity. Experiments were performed on in vitro spinal cord preparations from newborn rats (0 to 5 days). Rhythmic locomotor episodes (fictive locomotion) triggered by tonic electrical stimulations (2Hz, 30s) of a single sacral dorsal root were recorded from bilateral flexor-dominated (L2) and extensor-dominated (L5) ventral roots. We found that the activity pattern induced by sacral stimulation evolves over the 5 post-natal (P) day period. Although alternating rhythmic flexor-like motor bursts were expressed at all ages, the locomotor pattern of extensor-like bursting was progressively lost from P1 to P5. At later stages, serotonin (5-HT) and quipazine (5-HT2A receptor agonist) at concentrations sub-threshold for direct locomotor network activation promoted sacral stimulation-induced fictive locomotion. The 5-HT2A receptor antagonist ketanserin could reverse the agonist's action but was ineffective when fictive locomotion was already expressed in the absence of 5-HT (mainly before P2). Although inhibiting 5-HT7 receptors with SB266990 did not affect locomotor pattern organization, activating 5-HT1A receptors with 8-OH-DPAT specifically deteriorated extensor phase motor burst activity. We conclude that during the first 5 post-natal days in rat, serotonergic signaling in the lumbar cord becomes increasingly critical for the expression of fictive locomotion. Our findings therefore further underline the importance of both descending serotonergic and sensory afferent pathways in shaping locomotor activity during postnatal development.
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