Serotonin controls initiation of locomotion and afferent modulation of coordination via 5-HT7 receptors in adult rats

Abstract

Serotonergic (5-HT) pathways to the spinal cord are implicated in the control of locomotion based on studies using 5-HT₇ receptor agonists and antagonists and 5-HT₇ receptor knockout mice. Blockade of these receptors is thought to interfere with the activity of coordinating interneurons, a conclusion derived primarily from in vitro studies on isolated spinal cord of neonatal rats and mice. Developmental changes in the effects of 5-HT on spinal neurons have recently been described, and there is increasing data on control of sensory input by 5-HT₇ receptors on dorsal root ganglion cells and/or dorsal horn neurons, leading us to determine the effects of 5-HT₇ receptor blockade on voluntary overground locomotion and on locomotion without afferent input from the moving limb (fictive locomotion) in adult animals. Intrathecal injections of the selective 5-HT₇ antagonist SB269970 in adult intact rats suppressed locomotion by partial paralysis of hindlimbs. This occurred without a direct effect on motoneurons as revealed by an investigation of reflex activity. The antagonist disrupted intra- and interlimb coordination during locomotion in all intact animals but not during fictive locomotion induced by stimulation of the mesencephalic locomotor region (MLR). MLR evoked fictive locomotion was transiently blocked, then the amplitude and frequency of rhythmic activity was reduced by SB269970, consistent with the notion that the MLR activates 5-HT neurons, leading to excitation of CPG neurons with 5-HT₇ receptors. Effects on coordination in adults required the presence of afferent input, suggesting a switch to 5-HT₇ receptor mediated control of sensory pathways during development.

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