Spinal 5-HT7 receptors are critical for alternating activity during locomotion: in vitro neonatal and in vivo adult studies using 5-HT7 receptor knockout mice.
5-HT7 receptors have been implicated in the control of locomotion. Here we use 5-HT7 receptor knockout mice to rigorously test whether 5-HT acts at the 5-HT7 receptor to control locomotor-like activity in the neonatal mouse spinal cord in vitro and voluntary locomotion in adult mice. We found that 5-HT applied onto in vitro spinal cords of 5-HT7+/+ mice produced locomotor-like activity that was disrupted and subsequently blocked by the 5-HT7 receptor antagonist SB-269970. In spinal cords isolated from 5-HT7-/- mice, 5-HT produced either uncoordinated rhythmic activity or resulted in synchronous discharges of the ventral roots. SB-269970 had no effect on 5-HT-induced rhythmic activity in the 5-HT7-/- mice. In adult in vivo experiments, SB-269970 applied directly to the spinal cord consistently disrupted locomotion and produced prolonged-extension of the hindlimbs in 5-HT7+/+ but not 5-HT7-/- mice. Disrupted EMG activity produced by SB-269970 in vivo was similar to the uncoordinated rhythmic activity produced by the drug in vitro. Moreover, 5-HT7-/- mice displayed greater maximal extension at the hip and ankle joints than 5-HT7+/+ animals during voluntary locomotion. These results suggest that spinal 5-HT7 receptors are required for the production and coordination of 5-HT-induced locomotor-like activity in the neonatal mouse and are important for the coordination of voluntary locomotion in adult mice. We conclude that spinal 5-HT7 receptors are critical for alternating activity during locomotion.
Liu
Jun
J
Department of Physiology, The University of Manitoba Winnipeg, 730 William Avenue, BMSB 425, Winnipeg, Manitoba R3E 3J7 Canada.
Akay
Turgay
T
Hedlund
Peter B
PB
Pearson
Keir G
KG
Jordan
Larry M
LM
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D006614:Hindlimb / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007796:Laminectomy; D008124:Locomotion / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010636:Phenols / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000172:deficiency*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
D010636:Phenols; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D012701:Serotonin