Key pointsr Coordination of neuronal activity between left and right sides of the mammalian spinal cord is provided by several sets of commissural interneurons (CINs) whose axons cross the midline. Genetically identified inhibitory V0 D and excitatory V0 V CINs and ipsilaterally projecting excitatory V2a interneurons were shown to secure left-right alternation at different locomotor speeds.r We have developed computational models of neuronal circuits in the spinal cord that include left and right rhythm-generating centres interacting bilaterally via three parallel pathways mediated by V0 D , V2a-V0 V and V3 neuron populations.r The models reproduce the experimentally observed speed-dependent left-right coordination in normal mice and the changes in coordination seen in mutants lacking specific neuron classes.r The models propose an explanation for several experimental results and provide insights into the organization of the spinal locomotor network and parallel CIN pathways involved in gait control at different locomotor speeds.Abstract Different locomotor gaits in mammals, such as walking or galloping, are produced by coordinated activity in neuronal circuits in the spinal cord. Coordination of neuronal activity between left and right sides of the cord is provided by commissural interneurons (CINs), whose axons cross the midline. In this study, we construct and analyse two computational models of spinal locomotor circuits consisting of left and right rhythm generators interacting bilaterally via several neuronal pathways mediated by different CINs. The CIN populations incorporated in the models include the genetically identified inhibitory (V0 D ) and excitatory (V0 V ) subtypes of V0 CINs and excitatory V3 CINs. The model also includes the ipsilaterally projecting excitatory V2a interneurons mediating excitatory drive to the V0 V CINs. The proposed network architectures and CIN connectivity allow the models to closely reproduce and suggest mechanistic explanations for several experimental observations. These phenomena include: different speed-dependent contributions of V0 D and V0 V CINs and V2a interneurons to left-right alternation of neural activity, switching gaits between the left-right alternating walking-like activity and the left-right synchronous hopping-like pattern in mutants lacking specific neuron classes, and speed-dependent asymmetric changes of flexor and extensor phase durations. The models provide insights into the architecture of spinal network and the organization of parallel inhibitory and excitatory CIN pathways and suggest explanations for how these pathways maintain alternating and synchronous gaits at different locomotor speeds. The models propose testable predictions about the neural organization and operation of mammalian locomotor circuits.

The brainstem respiratory network can operate in multiple functional states engaging different statedependent neural mechanisms. These mechanisms were studied in the in situ perfused rat brainstemspinal cord preparation using sequential brainstem transections and administration of riluzole, a pharmacological blocker of persistent sodium current (I NaP ). Dramatic transformations in the rhythmogenic mechanisms and respiratory motor pattern were observed after removal of the pons and subsequent medullary transactions down to the rostral end of pre-Bötzinger complex (pre-BötC). A computational model of the brainstem respiratory network was developed to reproduce and explain these experimental findings. The model incorporates several interacting neuronal compartments, including the ventral respiratory group (VRG), pre-BötC, Bötzinger complex (BötC), and pons. Simulations mimicking the removal of circuit components following transections closely reproduce the respiratory motor output patterns recorded from the intact and sequentially reduced brainstem preparations. The model suggests that both the operating rhythmogenic mechanism (i.e., networkbased or pacemaker-driven) and the respiratory pattern generated (e.g., three-phase, two-phase, or one-phase) depend on the state of the pre-BötC (expression of I NaP -dependent intrinsic rhythmogenic mechanisms) and the BötC (providing expiratory inhibition in the network). At the same time, tonic drives from pons and multiple medullary chemoreceptive sites appear to control the state of these compartments and hence the operating rhythmogenic mechanism and motor pattern. Our results suggest that the brainstem respiratory network has a spatial (rostral-to-caudal) organization extending from the rostral pons to the VRG, in which each functional compartment is controlled by more rostral compartments. The model predicts a continuum of respiratory network states relying on different contributions of intrinsic cellular properties versus synaptic interactions for the generation and control of the respiratory rhythm and pattern.

A simple neuromechanical model has been developed that describes a spinal central pattern generator (CPG) controlling the locomotor movement of a single-joint limb via activation of two antagonist (flexor and extensor) muscles. The limb performs rhythmic movements under control of the muscular, gravitational and ground reaction forces. Muscle afferents provide length-dependent (types Ia and II) and force-dependent (type Ib from the extensor) feedback to the CPG. We show that afferent feedback adjusts CPG operation to the kinematics and dynamics of the limb providing stable “locomotion.” Increasing the supraspinal drive to the CPG increases locomotion speed by reducing the duration of stance phase. We show that such asymmetric, extensor-dominated control of locomotor speed (with relatively constant swing duration) is provided by afferent feedback independent of the asymmetric rhythmic pattern generated by the CPG alone (in “fictive locomotion” conditions). Finally, we demonstrate the possibility of reestablishing stable locomotion after removal of the supraspinal drive (associated with spinal cord injury) by increasing the weights of afferent inputs to the CPG, which is thought to occur following locomotor training.

Markin SN, Lemay MA, Prilutsky BI, Rybak IA. Motoneuronal and muscle synergies involved in cat hindlimb control during fictive and real locomotion: a comparison study. J Neurophysiol 107: 2057-2071, 2012. First published December 21, 2011 doi:10.1152/jn.00865.2011.-We compared the activity profiles and synergies of spinal motoneurons recorded during fictive locomotion evoked in immobilized decerebrate cat preparations by midbrain stimulation to the activity profiles and synergies of the corresponding hindlimb muscles obtained during forward level walking in cats. The fictive locomotion data were collected in the Spinal Cord Research Centre, University of Manitoba, and provided by Dr. David McCrea; the real locomotion data were obtained in the laboratories of M. A. Lemay and B. I. Prilutsky. Scatterplot representation and minimum spanning tree clustering algorithm were used to identify the possible motoneuronal and muscle synergies operating during both fictive and real locomotion. We found a close similarity between the activity profiles and synergies of motoneurons innervating one-joint muscles during fictive locomotion and the profiles and synergies of the corresponding muscles during real locomotion. However, the activity patterns of proximal nerves controlling two-joint muscles, such as posterior biceps and semitendinosus (PBSt) and rectus femoris (RF), were not uniform in fictive locomotion preparations and differed from the activity profiles of the corresponding two-joint muscles recorded during forward level walking. Moreover, the activity profiles of these nerves and the corresponding muscles were unique and could not be included in the synergies identified in fictive and real locomotion. We suggest that afferent feedback is involved in the regulation of locomotion via motoneuronal synergies controlled by the spinal central pattern generator (CPG) but may also directly affect the activity of motoneuronal pools serving two-joint muscles (e.g., PBSt and RF). These findings provide important insights into the organization of the spinal CPG in mammals, the motoneuronal and muscle synergies engaged during locomotion, and their afferent control. spinal cord; motoneurons; walking; one-joint muscles; two-joint muscles; cluster analysis THERE IS ACCUMULATING EVIDENCE that both higher brain centers and afferent feedback control motor behavior through the coordinated activation of specific groups of muscles referred to as synergies (Bernstein 1967;Bizzi et al. 2000Bizzi et al. , 2002Cappellini et al. 2006; d'Avella and Bizzi 2005;d'Avella et al. 2003d'Avella et al. , 2008Drew et al. 2008;Giszter et al. 2007; Giszter 2004, 2010;Kargo and Giszter 2008;Krouchev et al. 2006;McCrea 1992;Ting and Macpherson 2005;Tresch et al. 1999Tresch et al. , 2002 Tresch and Jarc 2009). According to this concept, the spinal cord contains populations of interneurons that project to, and simultaneously activate, specific populations of motoneurons that in turn actuate the specific groups of muscles (muscle synergies) producing a parti...

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