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This Article Full Text Full Text (PDF) All Versions of this Article: 102/1/337    most recent 91239.2008v2 91239.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Liu, J. Articles by Jordan, L. M. PubMed PubMed Citation Articles by Liu, J. Articles by Jordan, L. M.

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

¹Department of Physiology, University of Manitoba Winnipeg, Winnipeg, Canada; ²Centre for Neuroscience and Department of Physiology, University of Alberta, Edmonton, Canada.; ³Department of Molecular Biology, The Scripps Research Institute, La Jolla, California

Submitted 18 November 2008; accepted in final form 6 May 2009

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.

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