Epidural Spinal Cord Stimulation Plus Quipazine Administration Enable Stepping in Complete Spinal Adult Rats

• Published in: Journal of neurophysiology Vol. 98; no. 5; pp. 2525 - 2536
• Main Authors: Gerasimenko, Yury P, Ichiyama, Ronaldo M, Lavrov, Igor A, Courtine, Gregoire, Cai, Lance, Zhong, Hui, Roy, Roland R, Edgerton, V. Reggie
• Format: Journal Article
• Language: English
• Published: United States Am Phys Soc 01.11.2007
• Subjects: Animals; Behavior, Animal; Biomechanical Phenomena; Disease Models, Animal; Dose-Response Relationship, Drug; Electric Stimulation Therapy; Electrodes, Implanted; Electromyography - methods; Epidural Space; Female; Locomotion - drug effects; Locomotion - physiology; Locomotion - radiation effects; Motor Activity - drug effects; Motor Activity - radiation effects; Quipazine - administration & dosage; Rats; Rats, Sprague-Dawley; Reflex - drug effects; Reflex - radiation effects; Serotonin Receptor Agonists - administration & dosage; Spectrum Analysis; Spinal Cord - drug effects; Spinal Cord - physiology; Spinal Cord - radiation effects; Spinal Cord Injuries - therapy
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00836.2007

1 Departments of Physiological Science and 2 Neurobiology and 3 Brain Research Institute, University of California, Los Angeles, California; and 4 Pavlov Institute of Physiology, St. Petersburg, Russia Submitted 26 July 2007; accepted in final form 7 September 2007 We hypothesized that epidural spinal cord stimulation (ES) and quipazine (a serotonergic agonist) modulates the excitability of flexor and extensor related intraspinal neural networks in qualitatively unique, but complementary, ways to facilitate locomotion in spinal cord–injured rats. To test this hypothesis, we stimulated (40 Hz) the S 1 spinal segment before and after quipazine administration (0.3 mg/kg, ip) in bipedally step-trained and nontrained, adult, complete spinal (mid-thoracic) rats. The stepping pattern of these rats was compared with control rats. At the stimulation levels used, stepping was elicited only when the hindlimbs were placed on a moving treadmill. In nontrained rats, the stepping induced by ES and quipazine administration was non–weight bearing, and the cycle period was shorter than in controls. In contrast, the stepping induced by ES and quipazine in step-trained rats was highly coordinated with clear plantar foot placement and partial weight bearing. The effect of ES and quipazine on EMG burst amplitude and duration was greater in flexor than extensor motor pools. Using fast Fourier transformation analysis of EMG bursts during ES, we observed one dominant peak at 40 Hz in the medial gastrocnemius (ankle extensor), whereas there was less of dominant spectral peak in the tibialis anterior (ankle flexor). We suggest that these frequency distributions reflect amplitude modulation of predominantly monosynaptic potentials in the extensor and predominantly polysynaptic pathways in the flexor muscle. Quipazine potentiated the amplitude of these responses. The data suggest that there are fundamental differences in the circuitry that generates flexion and extension during locomotion. Address for reprint requests and other correspondence: V. R. Edgerton, Dept. of Physiological Science, Univ. of California, Los Angeles, CA 90095 (E-mail: vre{at}ucla.edu )