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Journal articles on the topic 'Spinal locomotor output'

Author: Grafiati

Published: 4 June 2025

Last updated: 15 July 2025

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1

Iwagaki, Noboru, and Gareth B. Miles. "Activation of group I metabotropic glutamate receptors modulates locomotor-related motoneuron output in mice." Journal of Neurophysiology 105, no. 5 (2011): 2108–20. http://dx.doi.org/10.1152/jn.01037.2010.

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Fast glutamatergic transmission via ionotropic receptors is critical for the generation of locomotion by spinal motor networks. In addition, glutamate can act via metabotropic glutamate receptors (mGluRs) to modulate the timing of ongoing locomotor activity. In the present study, we investigated whether mGluRs also modulate the intensity of motor output generated by spinal motor networks. Application of the group I mGluR agonist ( S)-3,5-dihydroxyphenylglycine (DHPG) reduced the amplitude and increased the frequency of locomotor-related motoneuron output recorded from the lumbar ventral roots

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Hayes, Heather Brant, Young-Hui Chang, and Shawn Hochman. "An In Vitro Spinal Cord–Hindlimb Preparation for Studying Behaviorally Relevant Rat Locomotor Function." Journal of Neurophysiology 101, no. 2 (2009): 1114–22. http://dx.doi.org/10.1152/jn.90523.2008.

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Although the spinal cord contains the pattern-generating circuitry for producing locomotion, sensory feedback reinforces and refines the spatiotemporal features of motor output to match environmental demands. In vitro preparations, such as the isolated rodent spinal cord, offer many advantages for investigating locomotor circuitry, but they lack the natural afferent feedback provided by ongoing locomotor movements. We developed a novel preparation consisting of an isolated in vitro neonatal rat spinal cord oriented dorsal-up with intact hindlimbs free to step on a custom-built treadmill. This

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Arber, Silvia, Ferreira Pinto Manuel Neves, Ludwig Ruder, and Paolo Capelli. "Connecting Circuits for Supraspinal Control of Locomotion." Neuron 100, no. 2 (2020): 361–74. https://doi.org/10.1016/j.neuron.2018.09.015.

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Locomotion is regulated by distributed circuits and achieved by the concerted activation of body musculature. While the basic properties of executive circuits in the spinal cord are fairly well understood, the precise mechanisms by which the brain impacts locomotion are much less clear. This Review discusses recent work unraveling the cellular identity, connectivity, and function of supraspinal circuits. We focus on their involvement in the regulation of the different phases of locomotion and their interaction with spinal circuits. Dedicated neuronal populations in the brainstem carry locomoto

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Gerasimenko, Yury, Ruslan Gorodnichev, Aleksandr Puhov, et al. "Initiation and modulation of locomotor circuitry output with multisite transcutaneous electrical stimulation of the spinal cord in noninjured humans." Journal of Neurophysiology 113, no. 3 (2015): 834–42. http://dx.doi.org/10.1152/jn.00609.2014.

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The mammalian lumbar spinal cord has the capability to generate locomotor activity in the absence of input from the brain. Previously, we reported that transcutaneous electrical stimulation of the spinal cord at vertebral level T11 can activate the locomotor circuitry in noninjured subjects when their legs are placed in a gravity-neutral position (Gorodnichev RM, Pivovarova EA, Pukhov A, Moiseev SA, Savokhin AA, Moshonkina TR, Shcherbakova NA, Kilimnik VA, Selionov VA, Kozlovskaia IB, Edgerton VR, Gerasimenko IU. Fiziol Cheloveka 38: 46–56, 2012). In the present study we hypothesized that stim

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5

Wilson, Jennifer M., Daniel A. Dombeck, Manuel Díaz-Ríos, Ronald M. Harris-Warrick, and Robert M. Brownstone. "Two-Photon Calcium Imaging of Network Activity in XFP-Expressing Neurons in the Mouse." Journal of Neurophysiology 97, no. 4 (2007): 3118–25. http://dx.doi.org/10.1152/jn.01207.2006.

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Fluorescent protein (XFP) expression in postnatal neurons allows the anatomical and physiological investigation of identified subpopulations of interneurons with established techniques. However, the spatiotemporal pattern of activity of these XFP neurons within a network and their role in the functional output of the network are more challenging issues to investigate. Here we apply two-photon excitation laser scanning microscopy to mouse spinal cord locomotor networks and present the methodology by which calcium activity can be recorded in XFP-expressing neurons. Such activity can be studied b

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Gerasimenko, Yury, Chet Preston, Hui Zhong, Roland R. Roy, V. Reggie Edgerton, and Prithvi K. Shah. "Rostral lumbar segments are the key controllers of hindlimb locomotor rhythmicity in the adult spinal rat." Journal of Neurophysiology 122, no. 2 (2019): 585–600. http://dx.doi.org/10.1152/jn.00810.2018.

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The precise location and functional organization of the spinal neuronal locomotor-related networks in adult mammals remain unclear. Our recent neurophysiological findings provided empirical evidence that the rostral lumbar spinal cord segments play a critical role in the initiation and generation of the rhythmic activation patterns necessary for hindlimb locomotion in adult spinal rats. Since added epidural stimulation at the S1 segments significantly enhanced the motor output generated by L2 stimulation, these data also suggested that the sacral spinal cord provides a strong facilitory influe

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Wannier, T., T. G. Deliagina, G. N. Orlovsky, and S. Grillner. "Differential Effects of the Reticulospinal System on Locomotion in Lamprey." Journal of Neurophysiology 80, no. 1 (1998): 103–12. http://dx.doi.org/10.1152/jn.1998.80.1.103.

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Wannier, T., T. G. Deliagina, G. N. Orlovsky, and S. Grillner. Differential effects of the reticulospinal system on locomotion in lamprey. J. Neurophysiol. 80: 103–112, 1998. Specific effects of stimulating different parts of the reticulospinal (RS) system on the spinal locomotor pattern are described in lamprey. In the in vitro brain stem and spinal cord preparation, microstimulation in different areas of the reticular formation was performed by ejecting a small amount of d-glutamate from a micropipette. These areas were distributed over the four reticular nuclei of the brain stem: the mesenc

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Beyeler, Anna, Charles Métais, Denis Combes, John Simmers, and Didier Le Ray. "Metamorphosis-Induced Changes in the Coupling of Spinal Thoraco-Lumbar Motor Outputs During Swimming in Xenopus laevis." Journal of Neurophysiology 100, no. 3 (2008): 1372–83. http://dx.doi.org/10.1152/jn.00023.2008.

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Anuran metamorphosis includes a complete remodeling of the animal's biomechanical apparatus, requiring a corresponding functional reorganization of underlying central neural circuitry. This involves changes that must occur in the coordination between the motor outputs of different spinal segments to harmonize locomotor and postural functions as the limbs grow and the tail regresses. In premetamorphic Xenopus laevis tadpoles, axial motor output drives rostrocaudally propagating segmental myotomal contractions that generate propulsive body undulations. During metamorphosis, the anterior axial mu

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Kawashima, Noritaka, Daichi Nozaki, Masaki O. Abe, and Kimitaka Nakazawa. "Shaping Appropriate Locomotive Motor Output Through Interlimb Neural Pathway Within Spinal Cord in Humans." Journal of Neurophysiology 99, no. 6 (2008): 2946–55. http://dx.doi.org/10.1152/jn.00020.2008.

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Direct evidence supporting the contribution of upper limb motion on the generation of locomotive motor output in humans is still limited. Here, we aimed to examine the effect of upper limb motion on locomotor-like muscle activities in the lower limb in persons with spinal cord injury (SCI). By imposing passive locomotion-like leg movements, all cervical incomplete ( n = 7) and thoracic complete SCI subjects ( n = 5) exhibited locomotor-like muscle activity in their paralyzed soleus muscles. Upper limb movements in thoracic complete SCI subjects did not affect the electromyographic (EMG) patter

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Dyck, Jason, Guillermo M. Lanuza, and Simon Gosgnach. "Functional characterization of dI6 interneurons in the neonatal mouse spinal cord." Journal of Neurophysiology 107, no. 12 (2012): 3256–66. http://dx.doi.org/10.1152/jn.01132.2011.

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Our understanding of the neural control of locomotion has been greatly enhanced by the ability to identify and manipulate genetically defined populations of interneurons that comprise the locomotor central pattern generator (CPG). To date, the dI6 interneurons are one of the few populations that settle in the ventral region of the postnatal spinal cord that have not been investigated. In the present study, we utilized a novel transgenic mouse line to electrophysiologically characterize dI6 interneurons located close to the central canal and study their function during fictive locomotion. The m

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Sławińska, Urszula, Krzysztof Miazga, and Larry Jordan. "The role of serotonin in the control of locomotor movements and strategies for restoring locomotion after spinal cord injury." Acta Neurobiologiae Experimentalis 74, no. 2 (2014): 172–87. http://dx.doi.org/10.55782/ane-2014-1983.

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In this review we will discuss different ways for re-establishing serotonergic activity that can enhance recovery of coordinated plantar stepping after spinal cord injury in adult rats. It is well known that serotoninergic neurons located in the medulla are able to initiate locomotor activity. This effect is exerted by actions on motoneurons and on neurons of the locomotor CPG (Central Pattern Generator). Motoneuron and interneuron excitability is increased, and putative CPG interneurons display oscillatory behaviour in response to serotonin receptor activation. The medullary serotonergic nucl

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Le Ray, Didier, Sandrine S. Bertrand, and Réjean Dubuc. "Cholinergic Modulation of Locomotor Circuits in Vertebrates." International Journal of Molecular Sciences 23, no. 18 (2022): 10738. http://dx.doi.org/10.3390/ijms231810738.

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Locomotion is a basic motor act essential for survival. Amongst other things, it allows animals to move in their environment to seek food, escape predators, or seek mates for reproduction. The neural mechanisms involved in the control of locomotion have been examined in many vertebrate species and a clearer picture is progressively emerging. The basic muscle synergies responsible for propulsion are generated by neural networks located in the spinal cord. In turn, descending supraspinal inputs are responsible for starting, maintaining, and stopping locomotion as well as for steering and control

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Liu, Jun, and Larry M. Jordan. "Stimulation of the Parapyramidal Region of the Neonatal Rat Brain Stem Produces Locomotor-Like Activity Involving Spinal 5-HT7 and 5-HT2A Receptors." Journal of Neurophysiology 94, no. 2 (2005): 1392–404. http://dx.doi.org/10.1152/jn.00136.2005.

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Locomotion can be induced in rodents by direct application 5-hydroxytryptamine (5-HT) onto the spinal cord. Previous studies suggest important roles for 5-HT7 and 5-HT2A receptors in the locomotor effects of 5-HT. Here we show for the first time that activation of a discrete population of 5-HT neurons in the rodent brain stem produces locomotion and that the evoked locomotion requires 5-HT7 and 5-HT2A receptors. Cells localized in the parapyramidal region (PPR) of the mid-medulla produced locomotor-like activity as a result of either electrical or chemical stimulation, and PPR-evoked locomotor

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14

Knikou, Maria. "Plasticity of Corticospinal Neural Control after Locomotor Training in Human Spinal Cord Injury." Neural Plasticity 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/254948.

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Spinal lesions substantially impair ambulation, occur generally in young and otherwise healthy individuals, and result in devastating effects on quality of life. Restoration of locomotion after damage to the spinal cord is challenging because axons of the damaged neurons do not regenerate spontaneously. Body-weight-supported treadmill training (BWSTT) is a therapeutic approach in which a person with a spinal cord injury (SCI) steps on a motorized treadmill while some body weight is removed through an upper body harness. BWSTT improves temporal gait parameters, muscle activation patterns, and c

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Miles, Gareth B., and Keith T. Sillar. "Neuromodulation of Vertebrate Locomotor Control Networks." Physiology 26, no. 6 (2011): 393–411. http://dx.doi.org/10.1152/physiol.00013.2011.

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Vertebrate locomotion must be adaptable in light of changing environmental, organismal, and developmental demands. Much of the underlying flexibility in the output of central pattern generating (CPG) networks of the spinal cord and brain stem is endowed by neuromodulation. This review provides a synthesis of current knowledge on the way that various neuromodulators modify the properties of and connections between CPG neurons to sculpt CPG network output during locomotion.

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Acton, David, and Gareth B. Miles. "Differential regulation of NMDA receptors by d-serine and glycine in mammalian spinal locomotor networks." Journal of Neurophysiology 117, no. 5 (2017): 1877–93. http://dx.doi.org/10.1152/jn.00810.2016.

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Activation of N-methyl-d-aspartate receptors (NMDARs) requires the binding of a coagonist, either d-serine or glycine, in addition to glutamate. Changes in occupancy of the coagonist binding site are proposed to modulate neural networks including those controlling swimming in frog tadpoles. Here, we characterize regulation of the NMDAR coagonist binding site in mammalian spinal locomotor networks. Blockade of NMDARs by d(−)-2-amino-5-phosphonopentanoic acid (d-APV) or 5,7-dichlorokynurenic acid reduced the frequency and amplitude of pharmacologically induced locomotor-related activity recorded

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Pulverenti, Timothy S., Md Anamul Islam, Ola Alsalman, Lynda M. Murray, Noam Y. Harel, and Maria Knikou. "Transspinal stimulation decreases corticospinal excitability and alters the function of spinal locomotor networks." Journal of Neurophysiology 122, no. 6 (2019): 2331–43. http://dx.doi.org/10.1152/jn.00554.2019.

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Locomotion requires the continuous integration of descending motor commands and sensory inputs from the legs by spinal central pattern generator circuits. Modulation of spinal neural circuits by transspinal stimulation is well documented, but how transspinal stimulation affects corticospinal excitability during walking in humans remains elusive. We measured the motor evoked potentials (MEPs) at multiple phases of the step cycle conditioned with transspinal stimulation delivered at sub- and suprathreshold intensities of the spinally mediated transspinal evoked potential (TEP). Transspinal stimu

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Higgin, Dwight, Alexander Krupka, Omid Haji Maghsoudi, et al. "Adaptation to slope in locomotor-trained spinal cats with intact and self-reinnervated lateral gastrocnemius and soleus muscles." Journal of Neurophysiology 123, no. 1 (2020): 70–89. http://dx.doi.org/10.1152/jn.00018.2019.

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Sensorimotor training providing motion-dependent somatosensory feedback to spinal locomotor networks restores treadmill weight-bearing stepping on flat surfaces in spinal cats. In this study, we examined if locomotor ability on flat surfaces transfers to sloped surfaces and the contribution of length-dependent sensory feedback from lateral gastrocnemius (LG) and soleus (Sol) to locomotor recovery after spinal transection and locomotor training. We compared kinematics and muscle activity at different slopes (±10° and ±25°) in spinalized cats ( n = 8) trained to walk on a flat treadmill. Half of

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Ménard, Ariane, and Sten Grillner. "Diencephalic Locomotor Region in the Lamprey—Afferents and Efferent Control." Journal of Neurophysiology 100, no. 3 (2008): 1343–53. http://dx.doi.org/10.1152/jn.01128.2007.

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In vertebrates, locomotion can be initiated by stimulation of the diencephalic locomotor region (DLR). Little is known of the different forebrain regions that provide input to the neurons in DLR. In the lamprey, it had been shown previously that DLR provides monosynaptic input to reticulospinal neurons, which in turn elicit rhythmic ventral root activity at the spinal level. To show that actual locomotor movements are produced from DLR, we use a semi-intact preparation in which the brain stem is exposed and the head fixed, while the body is left to generate actual swimming movements. DLR stimu

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Currie, Stephen P., Denis Combes, Nicholas W. Scott, John Simmers, and Keith T. Sillar. "A behaviorally related developmental switch in nitrergic modulation of locomotor rhythmogenesis in larval Xenopus tadpoles." Journal of Neurophysiology 115, no. 3 (2016): 1446–57. http://dx.doi.org/10.1152/jn.00283.2015.

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Locomotor control requires functional flexibility to support an animal's full behavioral repertoire. This flexibility is partly endowed by neuromodulators, allowing neural networks to generate a range of motor output configurations. In hatchling Xenopus tadpoles, before the onset of free-swimming behavior, the gaseous modulator nitric oxide (NO) inhibits locomotor output, shortening swim episodes and decreasing swim cycle frequency. While populations of nitrergic neurons are already present in the tadpole's brain stem at hatching, neurons positive for the NO-synthetic enzyme, NO synthase, subs

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Jean-Xavier, C., S. A. Sharples, K. A. Mayr, A. P. Lognon, and P. J. Whelan. "Retracing your footsteps: developmental insights to spinal network plasticity following injury." Journal of Neurophysiology 119, no. 2 (2018): 521–36. http://dx.doi.org/10.1152/jn.00575.2017.

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During development of the spinal cord, a precise interaction occurs between descending projections and sensory afferents, with spinal networks that lead to expression of coordinated motor output. In the rodent, during the last embryonic week, motor output first occurs as regular bursts of spontaneous activity, progressing to stochastic patterns of episodes that express bouts of coordinated rhythmic activity perinatally. Locomotor activity becomes functionally mature in the 2nd postnatal wk and is heralded by the onset of weight-bearing locomotion on the 8th and 9th postnatal day. Concomitantly

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Hayes, Heather Brant, Young-Hui Chang, and Shawn Hochman. "Stance-phase force on the opposite limb dictates swing-phase afferent presynaptic inhibition during locomotion." Journal of Neurophysiology 107, no. 11 (2012): 3168–80. http://dx.doi.org/10.1152/jn.01134.2011.

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Presynaptic inhibition is a powerful mechanism for selectively and dynamically gating sensory inputs entering the spinal cord. We investigated how hindlimb mechanics influence presynaptic inhibition during locomotion using pioneering approaches in an in vitro spinal cord–hindlimb preparation. We recorded lumbar dorsal root potentials to measure primary afferent depolarization-mediated presynaptic inhibition and compared their dependence on hindlimb endpoint forces, motor output, and joint kinematics. We found that stance-phase force on the opposite limb, particularly at toe contact, strongly i

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Buchanan, James T. "Spinal locomotor inputs to individually identified reticulospinal neurons in the lamprey." Journal of Neurophysiology 106, no. 5 (2011): 2346–57. http://dx.doi.org/10.1152/jn.01100.2010.

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Locomotor feedback signals from the spinal cord to descending brain stem neurons were examined in the lamprey using the uniquely identifiable reticulospinal neurons, the Müller and Mauthner cells. The same identified reticulospinal neurons were recorded in several preparations, under reduced conditions, to address whether an identified reticulospinal neuron shows similar locomotor-related oscillation timing from animal to animal and whether these timing signals can differ significantly from other identified reticulospinal neurons. Intracellular recordings of membrane potential in identified ne

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Wahlstrom-Helgren, Sarah, Jacob E. Montgomery, Kayce T. Vanpelt, Samantha L. Biltz, Jack H. Peck, and Mark A. Masino. "Glutamate receptor subtypes differentially contribute to optogenetically activated swimming in spinally transected zebrafish larvae." Journal of Neurophysiology 122, no. 6 (2019): 2414–26. http://dx.doi.org/10.1152/jn.00337.2019.

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The spinal cord (SC) contains neural networks that are capable of producing organized locomotor activity autonomously from the brain. Locomotor activity can be induced in spinally transected (spinalized) animals by adding a source of tonic excitation to activate spinal networks. This is commonly accomplished by activating N-methyl-d-aspartate (NMDA) glutamate receptors through bath application of NMDA. More recently, optogenetic approaches have enabled both activation and inactivation of neuronal cell populations to control the activity of locomotor networks. Larval zebrafish are exceptionally

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Foster, Joshua D., Catherine Dunford, Keith T. Sillar, and Gareth B. Miles. "Nitric oxide-mediated modulation of the murine locomotor network." Journal of Neurophysiology 111, no. 3 (2014): 659–74. http://dx.doi.org/10.1152/jn.00378.2013.

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Spinal motor control networks are regulated by neuromodulatory systems to allow adaptability of movements. The present study aimed to elucidate the role of nitric oxide (NO) in the modulation of mammalian spinal locomotor networks. This was investigated with isolated spinal cord preparations from neonatal mice in which rhythmic locomotor-related activity was induced pharmacologically. Bath application of the NO donor diethylamine NONOate (DEA/NO) decreased the frequency and modulated the amplitude of locomotor-related activity recorded from ventral roots. Removal of endogenous NO with coapplic

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Zhvansky, Dmitry S., Francesca Sylos-Labini, Arthur Dewolf, et al. "Evaluation of Spatiotemporal Patterns of the Spinal Muscle Coordination Output during Walking in the Exoskeleton." Sensors 22, no. 15 (2022): 5708. http://dx.doi.org/10.3390/s22155708.

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Recent advances in the performance and evaluation of walking in exoskeletons use various assessments based on kinematic/kinetic measurements. While such variables provide general characteristics of gait performance, only limited conclusions can be made about the neural control strategies. Moreover, some kinematic or kinetic parameters are a consequence of the control implemented on the exoskeleton. Therefore, standard indicators based on kinematic variables have limitations and need to be complemented by performance measures of muscle coordination and control strategy. Knowledge about what hap

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Picton, Laurence D., HongYan Zhang, and Keith T. Sillar. "Sodium pump regulation of locomotor control circuits." Journal of Neurophysiology 118, no. 2 (2017): 1070–81. http://dx.doi.org/10.1152/jn.00066.2017.

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Sodium pumps are ubiquitously expressed membrane proteins that extrude three Na+ ions in exchange for two K+ ions, using ATP as an energy source. Recent studies have illuminated additional, dynamic roles for sodium pumps in regulating the excitability of neuronal networks in an activity-dependent fashion. We review their role in a novel form of short-term memory within rhythmic locomotor networks. The data we review derives mainly from recent studies on Xenopus tadpoles and neonatal mice. The role and underlying mechanisms of pump action broadly match previously published data from an inverteb

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McMahon, Chantal, David P. Kowalski, Alexander J. Krupka, and Michel A. Lemay. "Single-cell and ensemble activity of lumbar intermediate and ventral horn interneurons in the spinal air-stepping cat." Journal of Neurophysiology 127, no. 1 (2022): 99–115. http://dx.doi.org/10.1152/jn.00202.2021.

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We report on the ensemble organization of interneuronal activity in the spinal cord during locomotor movements and show that lumbar intermediate zone interneurons organize in two groups related to the two major phases of walking: stance and swing. Ensemble organization is also shown to better correlate with muscular output than single-cell activity, although ensemble membership does not appear to be somatotopically organized within the spinal cord.

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MacKay-Lyons, Marilyn. "Central Pattern Generation of Locomotion: A Review of the Evidence." Physical Therapy 82, no. 1 (2002): 69–83. http://dx.doi.org/10.1093/ptj/82.1.69.

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Abstract Neural networks in the spinal cord, referred to as “central pattern generators” (CPGs), are capable of producing rhythmic movements, such as swimming, walking, and hopping, even when isolated from the brain and sensory inputs. This article reviews the evidence for CPGs governing locomotion and addresses other factors, including supraspinal, sensory, and neuromodulatory influences, that interact with CPGs to shape the final motor output. Supraspinal inputs play a major role not only in initiating locomotion but also in adapting the locomotor pattern to environmental and motivational co

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Kwan, Alex C., Shelby B. Dietz, Guisheng Zhong, Ronald M. Harris-Warrick, and Watt W. Webb. "Spatiotemporal Dynamics of Rhythmic Spinal Interneurons Measured With Two-Photon Calcium Imaging and Coherence Analysis." Journal of Neurophysiology 104, no. 6 (2010): 3323–33. http://dx.doi.org/10.1152/jn.00679.2010.

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In rhythmic neural circuits, a neuron often fires action potentials with a constant phase to the rhythm, a timing relationship that can be functionally significant. To characterize these phase preferences in a large-scale, cell type–specific manner, we adapted multitaper coherence analysis for two-photon calcium imaging. Analysis of simulated data showed that coherence is a simple and robust measure of rhythmicity for calcium imaging data. When applied to the neonatal mouse hindlimb spinal locomotor network, the phase relationships between peak activity of >1,000 ventral spinal interneurons

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Boyce, Vanessa S., and Michel A. Lemay. "Modularity of Endpoint Force Patterns Evoked Using Intraspinal Microstimulation in Treadmill Trained and/or Neurotrophin-Treated Chronic Spinal Cats." Journal of Neurophysiology 101, no. 3 (2009): 1309–20. http://dx.doi.org/10.1152/jn.00034.2008.

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Chronic spinal cats with neurotrophin-secreting fibroblasts (NTF) transplants recover locomotor function. To ascertain possible mechanisms, intraspinal microstimulation was used to examine the lumbar spinal cord motor output of four groups of chronic spinal cats: untrained cats with unmodified-fibroblasts graft (Op-control) or NTF graft and locomotor-trained cats with unmodified-fibroblasts graft (Trained) or NTF graft (Combination). Forces generated via intraspinal microstimulation at different hindlimb positions were recorded and interpolated, generating representations of force patterns at

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Ziskind-Conhaim, Lea, and Shawn Hochman. "Diversity of molecularly defined spinal interneurons engaged in mammalian locomotor pattern generation." Journal of Neurophysiology 118, no. 6 (2017): 2956–74. http://dx.doi.org/10.1152/jn.00322.2017.

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Mapping the expression of transcription factors in the mouse spinal cord has identified ten progenitor domains, four of which are cardinal classes of molecularly defined, ventrally located interneurons that are integrated in the locomotor circuitry. This review focuses on the properties of these interneuronal populations and their contribution to hindlimb locomotor central pattern generation. Interneuronal populations are categorized based on their excitatory or inhibitory functions and their axonal projections as predictors of their role in locomotor rhythm generation and coordination. The sy

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Leech, Kristan A., Hyosub E. Kim, and T. George Hornby. "Strategies to augment volitional and reflex function may improve locomotor capacity following incomplete spinal cord injury." Journal of Neurophysiology 119, no. 3 (2018): 894–903. http://dx.doi.org/10.1152/jn.00051.2017.

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Many studies highlight the remarkable plasticity demonstrated by spinal circuits following an incomplete spinal cord injury (SCI). Such plasticity can contribute to improvements in volitional motor recovery, such as walking function, although similar mechanisms underlying this recovery may also contribute to the manifestation of exaggerated responses to afferent input, or spastic behaviors. Rehabilitation interventions directed toward augmenting spinal excitability have shown some initial success in improving locomotor function. However, the potential effects of these strategies on involuntary

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Tresch, Matthew C., and Ole Kiehn. "Coding of Locomotor Phase in Populations of Neurons in Rostral and Caudal Segments of the Neonatal Rat Lumbar Spinal Cord." Journal of Neurophysiology 82, no. 6 (1999): 3563–74. http://dx.doi.org/10.1152/jn.1999.82.6.3563.

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Several experiments have demonstrated that rostral segments of the vertebrate lumbar spinal cord produce a rhythmic motor output more readily and of better quality than caudal segments. Here we examine how this rostrocaudal gradient of rhythmogenic capability is reflected in the spike activity of neurons in the rostral (L2) and caudal (L5) lumbar spinal cord of the neonatal rat. The spike activity of interneurons in the ventromedial cord, a region necessary for the production of locomotion, was recorded intracellularly with patch electrodes and extracellularly with tetrodes during pharmacologi

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Acton, David, Matthew J. Broadhead, and Gareth B. Miles. "Modulation of spinal motor networks by astrocyte-derived adenosine is dependent on D1-like dopamine receptor signaling." Journal of Neurophysiology 120, no. 3 (2018): 998–1009. http://dx.doi.org/10.1152/jn.00783.2017.

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Astrocytes modulate many neuronal networks, including spinal networks responsible for the generation of locomotor behavior. Astrocytic modulation of spinal motor circuits involves release of ATP from astrocytes, hydrolysis of ATP to adenosine, and subsequent activation of neuronal A1 adenosine receptors (A1Rs). The net effect of this pathway is a reduction in the frequency of locomotor-related activity. Recently, it was proposed that A1Rs modulate burst frequency by blocking the D1-like dopamine receptor (D1LR) signaling pathway; however, adenosine also modulates ventral horn circuits by dopam

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Dougherty, Kimberly J., Laskaro Zagoraiou, Daisuke Satoh, et al. "Locomotor Rhythm Generation Linked to the Output of Spinal Shox2 Excitatory Interneurons." Neuron 80, no. 4 (2013): 920–33. http://dx.doi.org/10.1016/j.neuron.2013.08.015.

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Martino, G., Y. Ivanenko, M. Serrao, et al. "Differential changes in the spinal segmental locomotor output in Hereditary Spastic Paraplegia." Clinical Neurophysiology 129, no. 3 (2018): 516–25. http://dx.doi.org/10.1016/j.clinph.2017.11.028.

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Humphreys, Jennifer M., and Patrick J. Whelan. "Dopamine exerts activation-dependent modulation of spinal locomotor circuits in the neonatal mouse." Journal of Neurophysiology 108, no. 12 (2012): 3370–81. http://dx.doi.org/10.1152/jn.00482.2012.

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Monoamines can modulate the output of a variety of invertebrate and vertebrate networks, including the spinal cord networks that control walking. Here we examined the multiple changes in the output of locomotor networks induced by dopamine (DA). We found that DA can depress the activation of locomotor networks in the neonatal mouse spinal cord following ventral root stimulation. By examining disinhibited rhythms, where the Renshaw cell pathway was blocked, we found that DA depresses a putative recurrent excitatory pathway that projects onto rhythm-generating circuitry of the spinal cord. This

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Shah, Prithvi K., and Igor Lavrov. "Spinal Epidural Stimulation Strategies: Clinical Implications of Locomotor Studies in Spinal Rats." Neuroscientist 23, no. 6 (2017): 664–80. http://dx.doi.org/10.1177/1073858417699554.

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Significant advancements in spinal epidural stimulation (ES) strategies to enable volitional motor control in persons with a complete spinal cord injury (SCI) have generated much excitement in the field of neurorehabilitation. Still, an obvious gap lies in the ability of ES to effectively generate a robust locomotor stepping response after a complete SCI in rodents, but not in humans. In order to reveal potential discrepancies between rodent and human studies that account for this void, in this review, we summarize the findings of studies that have utilized ES strategies to enable successful h

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Dewolf, A. H., Y. P. Ivanenko, K. E. Zelik, F. Lacquaniti, and P. A. Willems. "Differential activation of lumbar and sacral motor pools during walking at different speeds and slopes." Journal of Neurophysiology 122, no. 2 (2019): 872–87. http://dx.doi.org/10.1152/jn.00167.2019.

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Organization of spinal motor output has become of interest for investigating differential activation of lumbar and sacral motor pools during locomotor tasks. Motor pools are associated with functional grouping of motoneurons of the lower limb muscles. Here we examined how the spatiotemporal organization of lumbar and sacral motor pool activity during walking is orchestrated with slope of terrain and speed of progression. Ten subjects walked on an instrumented treadmill at different slopes and imposed speeds. Kinetics, kinematics, and electromyography of 16 lower limb muscles were recorded. The

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Gordon, Keith E., Ming Wu, Jennifer H. Kahn, and Brian D. Schmit. "Feedback and Feedforward Locomotor Adaptations to Ankle-Foot Load in People With Incomplete Spinal Cord Injury." Journal of Neurophysiology 104, no. 3 (2010): 1325–38. http://dx.doi.org/10.1152/jn.00604.2009.

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Humans with spinal cord injury (SCI) modulate locomotor output in response to limb load. Understanding the neural control mechanisms responsible for locomotor adaptation could provide a framework for selecting effective interventions. We quantified feedback and feedforward locomotor adaptations to limb load modulations in people with incomplete SCI. While subjects airstepped (stepping performed with kinematic assistance and 100% bodyweight support), a powered-orthosis created a dorisflexor torque during the “stance phase” of select steps producing highly controlled ankle-load perturbations. Wh

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Jinks, Steven L., Richard J. Atherley, Carmen L. Dominguez, Karen A. Sigvardt, and Joseph F. Antognini. "Isoflurane Disrupts Central Pattern Generator Activity and Coordination in the Lamprey Isolated Spinal Cord." Anesthesiology 103, no. 3 (2005): 567–75. http://dx.doi.org/10.1097/00000542-200509000-00020.

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Background Although volatile anesthetics such as isoflurane can depress sensory and motor neurons in the spinal cord, movement occurring during anesthesia can be coordinated, involving multiple limbs as well as the head and trunk. However, it is unclear whether volatile anesthetics depress locomotor interneurons comprising central pattern generators or disrupt intersegmental central pattern generator coordination. Methods Lamprey spinal cords were excised during anesthesia and placed in a bath containing artificial cerebrospinal fluid and D-glutamate to induce fictive swimming. The rostral, mi

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Dai, Yue, Yi Cheng, Brent Fedirchuk, Larry M. Jordan, and Junhao Chu. "Motoneuron output regulated by ionic channels: a modeling study of motoneuron frequency-current relationships during fictive locomotion." Journal of Neurophysiology 120, no. 4 (2018): 1840–58. http://dx.doi.org/10.1152/jn.00068.2018.

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Cat lumbar motoneurons display changes in membrane properties during fictive locomotion. These changes include reduction of input resistance and afterhyperpolarization, hyperpolarization of voltage threshold, and voltage-dependent excitation of the motoneurons. The state-dependent alteration of membrane properties leads to dramatic changes in frequency-current (F-I) relationship. The mechanism underlying these changes remains unknown. Using a motoneuron model combined with electrophysiological data, we investigated the channel mechanisms underlying the regulation of motoneuronal excitability a

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Smetana, R. W., S. Alford, and R. Dubuc. "Muscarinic Receptor Activation Elicits Sustained, Recurring Depolarizations in Reticulospinal Neurons." Journal of Neurophysiology 97, no. 5 (2007): 3181–92. http://dx.doi.org/10.1152/jn.00954.2006.

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In lampreys, brain stem reticulospinal (RS) neurons constitute the main descending input to the spinal cord and activate the spinal locomotor central pattern generators. Cholinergic nicotinic inputs activate RS neurons, and consequently, induce locomotion. Cholinergic muscarinic agonists also induce locomotion when applied to the brain stem of birds. This study examined whether bath applications of muscarinic agonists could activate RS neurons and initiate motor output in lampreys. Bath applications of 25 μM muscarine elicited sustained, recurring depolarizations (mean duration of 5.0 ± 0.5 s

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Lin, Shihao, Yaqing Li, Ana M. Lucas-Osma, et al. "Locomotor-related V3 interneurons initiate and coordinate muscles spasms after spinal cord injury." Journal of Neurophysiology 121, no. 4 (2019): 1352–67. http://dx.doi.org/10.1152/jn.00776.2018.

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Spinal cord injury leads to a devastating loss of motor function and yet is accompanied by a paradoxical emergence of muscle spasms, which often involve complex muscle activation patterns across multiple joints, reciprocal muscle timing, and rhythmic clonus. We investigated the hypothesis that spasms are a manifestation of partially recovered function in spinal central pattern-generating (CPG) circuits that normally coordinate complex postural and locomotor functions. We focused on the commissural propriospinal V3 neurons that coordinate interlimb movements during locomotion and examined mice

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Yazawa, Itaru, and Seiji Shioda. "Reciprocal functional interactions between the respiration/circulation center, the upper spinal cord, and the trigeminal system." Translational Neuroscience 6, no. 1 (2015): 87–102. http://dx.doi.org/10.1515/tnsci-2015-0008.

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AbstractThe interplay of neural discharge patterns involved in “respiration”, “circulation”, “opening movements in the mandible”, and “locomotion” was investigated electrophysiologically in a decerebrate and arterially perfused in situ rat preparation. Sympathetic tone increased with increases in perfusion flow rate. All nerve discharges became clearly organized into discharge episodes of increasing frequency and duration punctuated by quiescent periods as the perfusion flow rate increased at 26&#186;C. The modulated sympathetic tone at 10× total blood volume/ min activated the forelimb pa

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Zhang, Han, Dylan Deska-Gauthier, Colin S. MacKay, et al. "Widespread innervation of motoneurons by spinal V3 neurons globally amplifies locomotor output in mice." Cell Reports 44, no. 1 (2025): 115212. https://doi.org/10.1016/j.celrep.2024.115212.

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Witts, Emily C., Filipe Nascimento, and Gareth B. Miles. "Adenosine-mediated modulation of ventral horn interneurons and spinal motoneurons in neonatal mice." Journal of Neurophysiology 114, no. 4 (2015): 2305–15. http://dx.doi.org/10.1152/jn.00574.2014.

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Neuromodulation allows neural networks to adapt to varying environmental and biomechanical demands. Purinergic signaling is known to be an important modulatory system in many parts of the CNS, including motor control circuitry. We have recently shown that adenosine modulates the output of mammalian spinal locomotor control circuitry (Witts EC, Panetta KM, Miles GB. J Neurophysiol 107: 1925–1934, 2012). Here we investigated the cellular mechanisms underlying this adenosine-mediated modulation. Whole cell patch-clamp recordings were performed on ventral horn interneurons and motoneurons within i

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Kiehn, Ole, Keith T. Sillar, Ole Kjaerulff, and Jonathan R. McDearmid. "Effects of Noradrenaline on Locomotor Rhythm–Generating Networks in the Isolated Neonatal Rat Spinal Cord." Journal of Neurophysiology 82, no. 2 (1999): 741–46. http://dx.doi.org/10.1152/jn.1999.82.2.741.

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We have studied the effects of the biogenic amine noradrenaline (NA) on motor activity in the isolated neonatal rat spinal cord. The motor output was recorded with suction electrodes from the lumbar ventral roots. When applied on its own, NA (0.5–50 μM) elicited either no measurable root activity, or activity of a highly variable nature. When present, the NA-induced activity consisted of either low levels of unpatterned tonic discharges, or an often irregular, slow rhythm that displayed a high degree of synchrony between antagonistic motor pools. Finally, in a few cases, NA induced a slow loco

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Dai, Yue, Kevin P. Carlin, Zongming Li, Douglas G. McMahon, Robert M. Brownstone, and Larry M. Jordan. "Electrophysiological and Pharmacological Properties of Locomotor Activity-Related Neurons in cfos-EGFP Mice." Journal of Neurophysiology 102, no. 6 (2009): 3365–83. http://dx.doi.org/10.1152/jn.00265.2009.

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Although locomotion is known to be generated by networks of spinal neurons, knowledge of the properties of these neurons is limited. Using neonatal transgenic mice that express enhanced green fluorescent protein (EGFP) driven by the c-fos promoter, we visualized EGFP-positive neurons in spinal cord slices from animals that were subjected to a locomotor task or drug cocktail [ N-methyl-d-aspartate, serotonin (5-HT), dopamine, and acetylcholine (ACh)]. The activity-dependent expression of EGFP was also induced in dorsal root ganglion neurons with electrical stimulation of the neurons. Following

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