599 0097-0549/20/5005-0599 ©2020 Springer Science+Business Media, LLC Neuroscience and Behavioral Physiology, Vol. 50, No. 5, June, 2020 Restoration of Motor Functions in Spinal Rats by Electrical Stimulation of the Spinal Cord and Locomotor Training N. V. Pavlova, 1,2 I. N. Bogacheva, 1 E. Yu. Bazhenova, 1 O. V. Gorsky, 1 T. R. Moshonkina, 1 and Yu. P. Gerasimenko 1 Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 105, No. 5, pp. 565–577, May, 2019. Original article submitted March 7, 2019. Revised version received March 24, 2019. Accepted March 25, 2019. The recovery of motor functions in chronic spinal rats with locomotor training on a treadmill combined with electrical stimulation of the spinal cord was studied. Training to a bipedal gait on a moving band with the body weight supported and use of either subcutaneous or epidural electrical stimulation (40 Hz) was performed for five days per week for 20–30 min. The dynamics of changes in locomotor capacity using subcutaneous and epidural electrical stimulation and their actions on the neural structures of the spinal cord could be similar. After three weeks of motor rehabilitation, a single stimulation at a frequency of 1 Hz evoked reflex monosynaptic potentials in the hindlimb muscles, while simultaneous rhythmic stimulation of two loci in the spinal cord at a frequency of 40 Hz initiated locomotor-like activity on the moving band of the treadmill. A more marked rhythm was seen after nine weeks of training, which coincided with the appearance of polysynaptic spinal reflexes. Administration of the serotonin receptor agonist quipazine en- hanced polysynaptic activity in reflex responses and improved locomotion. Use of noninvasive subcutane- ous stimulation in combination with locomotor training was found to be an effective method of activating neural locomotor networks to an extent comparable to that obtained with invasive epidural stimulation. Keywords: spinal cord, electrical stimulation, training, locomotor response. Electrical stimulation of the spinal cord in humans and animals has been actively used in recent years in physiolog- ical research and clinical practice. In physiological studies, electrical epidural stimulation of the spinal cord (ESSC) has been used to address the visceral [1] and somatic centers located in the spinal cord, including the spinal locomotor networks [2–4]. Electrophysiological and histological ex- periments have shown that ESSC acts on the dorsal roots, activating mono- and polysynaptic neural networks, which produce the stepping pattern addressed to motoneurons [5, 6]. Recent studies have shown that transcutaneous stim- ulation of the spinal cord in the area of the lumbar bulge in- duces a locomotor response in healthy volunteers [7]. On the one hand, use of noninvasive stimulation allowed electrical stimulation of the spinal cord to be applied in healthy people and provided for use of this method in physiological studies of the spinal cord in health; on the other hand, a noninva- sive means of stimulating the spinal cord was found and this has already seen clinical use [8, 9]. The challenge is that on transcutaneous stimulation of the spinal cord, there are sev- eral types of biological tissue between the stimulating elec- trode and the spinal cord and these have different electrical conductivities, so it is quite difficult to predict which spinal cord structures will be activated by this stimulation method. The task addressed in the present study was to compare, in a single experiment, the reflex activity of the rat spinal cord to ESSC and transcutaneous stimulation of the spinal cord; we also evaluated the rehabilitation potential of these two methods. Given that the studies were performed in chronic experiments in the animals, transcutaneous stimulation was replaced with subcutaneous stimulation of the spinal cord 1 Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia; e-mail: boiss@mail.ru. 2 Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia. DOI 10.1007/s11055-020-00941-y