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Spinal Cord-Transected Mice Learn to Step in Response to Quipazine Treatment and Robotic Training

Fong, Andy J. and Cai, Lance L. and Otoshi, Chad K. and Reinkensmeyer, David J. and Burdick, Joel W. and Roy, Roland R. and Edgerton, V. Reggie (2005) Spinal Cord-Transected Mice Learn to Step in Response to Quipazine Treatment and Robotic Training. Journal of Neuroscience, 25 (50). pp. 11738-11747. ISSN 0270-6474.

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In the present study, concurrent treatment with robotic step training and a serotonin agonist, quipazine, generated significant recovery of locomotor function in complete spinal cord-transected mice (T7–T9) that otherwise could not step. The extent of recovery achieved when these treatments were combined exceeded that obtained when either treatment was applied independently. We quantitatively analyzed the stepping characteristics of spinal mice after alternatively administering no training, manual training, robotic training, quipazine treatment, or a combination of robotic training with quipazine treatment, to examine the mechanisms by which training and quipazine treatment promote functional recovery. Using fast Fourier transform and principal components analysis, significant improvements in the step rhythm, step shape consistency, and number of weight-bearing steps were observed in robotically trained compared with manually trained or nontrained mice. In contrast, manual training had no effect on stepping performance, yielding no improvement compared with nontrained mice. Daily bolus quipazine treatment acutely improved the step shape consistency and number of steps executed by both robotically trained and nontrained mice, but these improvements did not persist after quipazine was withdrawn. At the dosage used (0.5 mg/kg body weight), quipazine appeared to facilitate, rather than directly generate, stepping, by enabling the spinal cord neural circuitry to process specific patterns of sensory information associated with weight-bearing stepping. Via this mechanism, quipazine treatment enhanced kinematically appropriate robotic training. When administered intermittently during an extended period of robotic training, quipazine revealed training-induced stepping improvements that were masked in the absence of the pharmacological treatment.

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Additional Information:© 2005 Society for Neuroscience. Beginning six months after publication the Work will be made freely available to the public on SfN’s website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license ( Received Aug. 6, 2004; revised Oct. 27, 2005; accepted Nov. 5, 2005. This research was supported by the Christopher Reeve Foundation, National Institute of Child Health and Human Development/National Institute of Neurological Disorders and Stroke Grant HD44830, the National Institute of Neurological Disorders and Stroke Grant NS16333, the Roman Reed Spinal Cord Injury Research Funds, and the University of California, Los Angeles Academic Senate. We thank the following: Hui Zhong for her assistance with animal surgeries; Maynor Herrera for providing excellent animal care; Mark Merlo for designing and fabricating the first prototype of the mouse robot; Niranjala Tillakaratne, John Hodgson, Rebekah Molyneux, and Sharon Zdunowski for their constructive comments and valuable discussions; and an incredible team of undergraduate students, Vivek Agarwal, Nikhil Daga, Gary Hsu, Jee Hur, Dan Popa, Tony Tzeng, Elizabeth Waters, and Yvonne Yaory, for all of their hard work.
Funding AgencyGrant Number
Christopher Reeve FoundationUNSPECIFIED
Roman Reed Spinal Cord Injury Research FundsUNSPECIFIED
Subject Keywords:Locomotion; quipazine; serotonin; robotics; spinal cord injury; SCI; motor learning; training; plasticity
Issue or Number:50
Record Number:CaltechAUTHORS:20190614-161544893
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Official Citation:Andy J. Fong, Lance L. Cai, Chad K. Otoshi, David J. Reinkensmeyer, Joel W. Burdick, Roland R. Roy and V. Reggie Edgerton Journal of Neuroscience 14 December 2005, 25 (50) 11738-11747; DOI:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:96454
Deposited By: Melissa Ray
Deposited On:14 Jun 2019 23:46
Last Modified:03 Oct 2019 21:22

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