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

• Published in: Journal of neurophysiology Vol. 102; no. 1; pp. 337 - 348
• Main Authors: Liu, Jun, Akay, Turgay, Hedlund, Peter B, Pearson, Keir G, Jordan, Larry M
• Format: Journal Article
• Language: English
• Published: United States Am Phys Soc 01.07.2009
• Subjects: Action Potentials - drug effects; Action Potentials - genetics; Animals; Animals, Newborn; Dose-Response Relationship, Drug; Electromyography; Functional Laterality - drug effects; Functional Laterality - physiology; Hindlimb - drug effects; Hindlimb - physiology; In Vitro Techniques; Laminectomy; Locomotion - drug effects; Locomotion - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Phenols - pharmacology; Receptors, Serotonin - deficiency; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Spinal Cord - drug effects; Spinal Cord - growth & development; Spinal Cord - metabolism; Spinal Cord - physiology; Sulfonamides - pharmacology; Time Factors
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.91239.2008

1 Department of Physiology, University of Manitoba Winnipeg, Winnipeg, Canada; 2 Centre for Neuroscience and Department of Physiology, University of Alberta, Edmonton, Canada.; 3 Department of Molecular Biology, The Scripps Research Institute, La Jolla, California Submitted 18 November 2008; accepted in final form 6 May 2009 5-HT 7 receptors have been implicated in the control of locomotion. Here we use 5-HT 7 receptor knockout mice to rigorously test whether 5-HT acts at the 5-HT 7 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-HT 7 +/+ mice produced locomotor-like activity that was disrupted and subsequently blocked by the 5-HT 7 receptor antagonist SB-269970. In spinal cords isolated from 5-HT 7 –/– 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-HT 7 –/– 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-HT 7 +/+ but not 5-HT 7 –/– 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-HT 7 –/– mice displayed greater maximal extension at the hip and ankle joints than 5-HT 7 +/+ animals during voluntary locomotion. These results suggest that spinal 5-HT 7 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-HT 7 receptors are critical for alternating activity during locomotion. Address for reprint requests and other correspondence: L. M. Jordan, Dept. of Physiology, The University of Manitoba, 730 William Avenue, BMSB 425, Winnipeg, Manitoba R3E 3J7 Canada (E-mail: larry{at}scrc.umanitoba.ca )