Abstract
Activation of the serotonin system has been shown to induce locomotor activity following a spinal cord transection. This study examines how the isolated spinal cord adapts to a sensory perturbation during activation of the serotonergic system. Real-time and persistent effects of a perturbation were examined in intact and spinal transected newborn rats. Rats received a spinal surgery (sham or low thoracic transection) on postnatal day 1 and were tested 9 days later. At test, subjects were treated with the serotonergic receptor agonist quipazine (3.0 mg/kg) to induce stepping behavior. Half of the subjects experienced range of motion (ROM) restriction during stepping, while the other half did not. Differences in stepping behavior (interlimb coordination) and limb trajectories (intralimb coordination) were found to occur in both intact and spinal subjects. Adaptations were seen in the forelimbs and hindlimbs. Also, real-time and persistent effects of ROM restriction (following removal of the perturbation) were seen in ROM-restricted subjects. This study demonstrates the sensitivity of the isolated spinal cord to sensory feedback in conjunction with serotonin modulation.
Highlights
The role of serotonin (5-HT) in the activation and modulation of spinal locomotor circuits is well known, and has been demonstrated at the anatomical, neurophysiological, and behavioral levels of analysis. 5-HT receptors are found in high concentrations in locomotor regions of the spinal cord such as the cervical and lumbar enlargements (Jankowska et al, 1995, 1999), and bath application of 5-HT induces fictive locomotion in the spinal cord and spinal cord slices in vitro (e.g., Cowley and Schmidt, 1994; Garraway and Hochman, 2001; Hayes et al, 2008)
Findings from this study suggest that the immature, isolated spinal cord modulates inter- and intralimb coordination in response to sensory feedback during locomotor activity induced by serotonergic stimulation
We found that the spinal cord is able to support persistent behavioral changes after exposure to a sensorimotor perturbation
Summary
The role of serotonin (5-HT) in the activation and modulation of spinal locomotor circuits is well known, and has been demonstrated at the anatomical, neurophysiological, and behavioral levels of analysis. 5-HT receptors are found in high concentrations in locomotor regions of the spinal cord such as the cervical and lumbar enlargements (Jankowska et al, 1995, 1999), and bath application of 5-HT induces fictive locomotion in the spinal cord and spinal cord slices in vitro (e.g., Cowley and Schmidt, 1994; Garraway and Hochman, 2001; Hayes et al, 2008). During fictive locomotion induced by stimulation of the mesencephalic locomotor region, serotonergic boutons containing 5-HT7, 5-HT2A, and 5-HT1A receptors were found to form synapses with or were in close proximity to activated lumbar motor neurons in the cat (Noga et al, 2009). 5-HT receptor antagonists reduce locomotor activity produced by 5-HT treatment or electrical stimulation of the parapyramidal region (Cazalets et al, 1992; Liu and Jordan, 2005; Kao et al, 2006). Taken together, these studies point to an active role of the serotonergic system in modulating locomotor circuit activity
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