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The Journal of Neuroscience, July 16, 2008, 28(29):7370-7375; doi:10.1523/JNEUROSCI.1881-08.2008

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Brief Communications
Step Training Reinforces Specific Spinal Locomotor Circuitry in Adult Spinal Rats

Ronaldo M. Ichiyama,^1,3 Grégoire Courtine,^2,3 Yury P. Gerasimenko,^3,6 Grace J. Yang,³ Rubia van den Brand,^2,3 Igor A. Lavrov,³ Hui Zhong,³ Roland R. Roy,^3,4 and V. Reggie Edgerton^3,4,5

¹Institute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, United Kingdom, ²Experimental Neurorehabilitation Laboratory, University of Zurich, CH-8032 Zurich, Switzerland, Departments of ³Physiological Science and ⁴Neurobiology and ⁵Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90095, and ⁶Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg 199034, Russia

Correspondence should be addressed to Dr. Ronaldo M. Ichiyama, Institute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, UK. Email: r.m.ichiyama{at}leeds.ac.uk

Locomotor training improves function after a spinal cord injury both in experimental and clinical settings. The activity-dependent mechanisms underlying such improvement, however, are sparsely understood. Adult rats received a complete spinal cord transection (T9), and epidural stimulation (ES) electrodes were secured to the dura matter at L2. EMG electrodes were implanted bilaterally in selected muscles. Using a servo-controlled body weight support system for bipedal stepping, five rats were trained 7 d/week for 6 weeks (30 min/d) under quipazine (0.3 mg/kg) and ES (L2; 40 Hz). Nontrained rats were handled as trained rats but did not receive quipazine or ES. At the end of the experiment, a subset of rats was used for c-fos immunohistochemistry. Three trained and three nontrained rats stepped for 1 h (ES; no quipazine) and were returned to their cages for 1 h before intracardiac perfusion. All rats could step with ES and quipazine administration. The trained rats had higher and longer steps, narrower base of support at stance, and lower variability in EMG parameters than nontrained rats, and these properties approached that of noninjured controls. After 1 h of stepping, the number of FOS+ neurons was significantly lower in trained than nontrained rats throughout the extent of the lumbosacral segments. These results suggest that training reinforces the efficacy of specific sensorimotor pathways, resulting in a more selective and stable network of neurons that controls locomotion.

Key words: epidural electrical stimulation; locomotion; spinal cord; rats; training; c-fos

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Received Feb. 27, 2008; revised May 30, 2008; accepted June 2, 2008.

Correspondence should be addressed to Dr. Ronaldo M. Ichiyama, Institute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, UK. Email: r.m.ichiyama{at}leeds.ac.uk

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