title: Epidural spinal cord stimulation plus quipazine administration enable stepping in complete spinal adult rats.
abstract: 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.
authors.affiliation: Department of Physiological Science, University of California, Los Angeles, CA 90095, USA.
authors.forename: Yury P
authors.initials: YP
authors.lastname: Gerasimenko
authors.forename: Ronaldo M
authors.initials: RM
authors.lastname: Ichiyama
authors.forename: Igor A
authors.initials: IA
authors.lastname: Lavrov
authors.forename: Gregoire
authors.initials: G
authors.lastname: Courtine
authors.forename: Lance
authors.initials: L
authors.lastname: Cai
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
authors.forename: Roland R
authors.initials: RR
authors.lastname: Roy
authors.forename: V Reggie
authors.initials: VR
authors.lastname: Edgerton
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001696:Biomechanical Phenomena; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004599:Electric Stimulation Therapy; D004567:Electrodes, Implanted; D004576:Electromyography / Q000379:methods; D004824:Epidural Space; D005260:Female; D008124:Locomotion / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009043:Motor Activity / Q000187:drug effects / Q000528:radiation effects; D011814:Quipazine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects / Q000528:radiation effects; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage*; D013057:Spectrum Analysis; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013119:Spinal Cord Injuries / Q000628:therapy*
chemical_list: D017366:Serotonin Receptor Agonists; D011814:Quipazine