title: Serotonin controls initiation of locomotion and afferent modulation of coordination via 5-HT7receptors in adult rats.
abstract: Experiments on neonatal rodent spinal cord showed that serotonin (5-HT), acting via 5-HT7receptors, is required for initiation of locomotion and for controlling the action of interneurons responsible for inter- and intralimb coordination, but the importance of the 5-HT system in adult locomotion is not clear. Blockade of spinal 5-HT7receptors interfered with voluntary locomotion in adult rats and fictive locomotion in paralysed decerebrate rats with no afferent feedback, consistent with a requirement for activation of descending 5-HT neurons for production of locomotion. The direct control of coordinating interneurons by 5-HT7receptors observed in neonatal animals was not found during fictive locomotion, revealing a developmental shift from direct control of locomotor interneurons in neonates to control of afferent input from the moving limb in adults. An understanding of the afferents controlled by 5-HT during locomotion is required for optimal use of rehabilitation therapies involving the use of serotonergic drugs.
  
  
  
  Serotonergic pathways to the spinal cord are implicated in the control of locomotion based on studies using serotonin type 7 (5-HT7) receptor agonists and antagonists and 5-HT7receptor 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 serotonin (5-HT) on spinal neurons have recently been described, and there is increasing data on control of sensory input by 5-HT7receptors on dorsal root ganglion cells and/or dorsal horn neurons, leading us to determine the effects of 5-HT7receptor 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-HT7antagonist 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 were reduced by SB269970, consistent with the notion that the MLR activates 5-HT neurons, leading to excitation of central pattern generator neurons with 5-HT7receptors. Effects on coordination in adults required the presence of afferent input, suggesting a switch to 5-HT7receptor-mediated control of sensory pathways during development.
authors.affiliation: Department of Neurophysiology, Nencki Institute of Experimental Biology PAS, 02-093, Warsaw, Poland.|Department of Nerve-Muscle Engineering, Institute of Biocybernetics and Biomedical Engineering PAS, 02-109, Warsaw, Poland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Cabaj
authors.affiliation: Department of Neurophysiology, Nencki Institute of Experimental Biology PAS, 02-093, Warsaw, Poland.
authors.forename: Henryk
authors.initials: H
authors.lastname: Majczyński
authors.affiliation: Department of Physiology & Pathophysiology, Spinal Cord Research Centre, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada.
authors.forename: Erika
authors.initials: E
authors.lastname: Couto
authors.affiliation: Department of Physiology & Pathophysiology, Spinal Cord Research Centre, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada.
authors.forename: Phillip F
authors.initials: PF
authors.lastname: Gardiner
authors.affiliation: Department of Physiology & Pathophysiology, Spinal Cord Research Centre, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada.
authors.forename: Katinka
authors.initials: K
authors.lastname: Stecina
authors.affiliation: Department of Neurophysiology, Nencki Institute of Experimental Biology PAS, 02-093, Warsaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Sławińska
authors.affiliation: Department of Physiology & Pathophysiology, Spinal Cord Research Centre, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada.
authors.forename: Larry M
authors.identifier: 0000-0003-2501-4276
authors.initials: LM
authors.lastname: Jordan
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D005260:Female; D006614:Hindlimb / Q000502:physiology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D010636:Phenols / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000235:genetics / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D010636:Phenols; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D012701:Serotonin
keywords: fictive locomotion; serotonin; voluntary locomotion