Spinal Central Pattern Generator Research Articles

Investigation of central pattern generators in the spinal cord of chicken embryos.

For most quadrupeds, locomotion involves alternating movements of the fore- and hindlimbs. In birds, however, while walking generally involves alternating movements of the legs, to generate lift and thrust, the wings are moved synchronously with each other. Neural circuits in the spinal cord, referred to as central pattern generators (CPGs), are the source of the basic locomotor rhythms and patterns. Given the differences in the patterns of movement of the wings and legs, it is likely that the neuronal components and connectivity of the CPG that coordinates wing movements differ from those that coordinate leg movements. In this study, we used in vitro preparations of embryonic chicken spinal cords (E11-E14) to compare the neural responses of spinal CPGs that control and coordinate wing flapping with those that control alternating leg movements. We found that in response to N-methyl-D-aspartate (NMDA) or a combination of NMDA and serotonin (5-HT), the intact chicken spinal cord produced rhythmic outputs that were synchronous both bilaterally and between the wing and leg segments. Despite this, we found that this rhythmic output was disrupted by an antagonist of glycine receptors in the lumbosacral (legs), but not the brachial (wing) segments. Thus, our results provide evidence of differences between CPGs that control the wings and legs in the spinal cord of birds.

Can a Plegic Leg Move Itself?

The spinal cord is responsible for several types of involuntary movements, from segmental spinal myoclonus to stepping automated movements generated by spinal central pattern generators (CPG). We present the case of a 47-year-old inpatient woman admitted for suspected spondylodiscitis. Immediate neurologic evaluation was requested in day 2 due to involuntary movements. The neurological examination revealed paraplegia with hyperreflexia, bilateral Babinski’s sign, thermal-algic and tactile sensory level by T5 and proprioceptive compromise of the lower limbs. Involuntary, stimulus-sensitive, wide, rhythmic and stereotyped movements of the left lower limb were observed, involving several muscle groups, similar to stepping movements. Further investigation documented myelopathy secondary to dorsal extradural lesion D2-D3, whose excision led to the complete resolution of these movements. Given the characteristics of these movements, we assume that they are stepping automatism movements generated by CPG.

Astrocytic Kir4.1 channels regulate locomotion by orchestrating neuronal rhythmicity in the spinal network.

Neuronal rhythmogenesis in the spinal cord is correlated with variations in extracellular K+ levels ([K+ ]e ). Astrocytes play important role in [K+ ]e homeostasis and compute neuronal information. Yet it is unclear how neuronal oscillations are regulated by astrocytic K+ homeostasis. Here we identify the astrocytic inward-rectifying K+ channel Kir4.1 (a.k.a. Kcnj10) as a key molecular player for neuronal rhythmicity in the spinal central pattern generator (CPG). By combining two-photon calcium imaging with electrophysiology, immunohistochemistry and genetic tools, we report that astrocytes display Ca2+ transients before and during oscillations of neighboring neurons. Inhibition of astrocytic Ca2+ transients with BAPTA decreases the barium-sensitive Kir4.1 current responsible of K+ clearance. Finally, we show in mice that Kir4.1 knockdown in astrocytes progressively prevents neuronal oscillations and alters the locomotor pattern resulting in lower motor performances in challenging tasks. These data identify astroglial Kir4.1 channels as key regulators of neuronal rhythmogenesis in the CPG driving locomotion.

Chapter 2 - Upper and lower motor neuron neurophysiology and motor control

This chapter considers the principles that underlie neurophysiological studies of upper motor neuron or lower motor neuron lesions, based on an understanding of the normal structure and function of the motor system. Human motor neurophysiology consists of an evaluation of the active components of the motor system that are relevant to volitional movements. Relatively primitive motor skills include locomotion, much dependent on the spinal cord central pattern generator, reaching, involving proximal and distal muscles activation, and grasping. Humans are well prepared to perform complex movements like writing. The role of motor cortex is critical for the motor activity, very dependent on the continuous sensory feedback, and this is essential for adapting the force and speed control, which contributes to motor learning. Most corticospinal neurons in the brain project to brainstem and spinal cord, many with polysynaptic inhibitory rather than excitatory connections. The monosynaptic connections observed in humans and primates constitute a specialized pathway implicated in fractional finger movements. Spinal cord has a complex physiology, and local reflexes and sensory feedback are essential to control adapted muscular contraction during movement. The cerebellum has a major role in motor coordination, but also consistent roles in sensory activities, speech, and language, in motor and spatial memory, and in psychological activity. The motor unit is the final effector of the motor drive. The complex interplay between the lower motor neuron, its axon, motor end-plates, and muscle fibers allows a relevant plasticity in the movement output.

Firing behavior of single motor units of the tibialis anterior in human walking as non-invasively revealed by HDsEMG decomposition

Objective. Investigation of the firing behavior of motor units (MUs) provides essential neuromuscular control information because MUs are the smallest organizational component of the neuromuscular system. The MUs activated during human infants’ leg movements and rodent locomotion, mainly controlled by the spinal central pattern generator (CPG), show highly synchronous firing. In addition to spinal CPGs, the cerebral cortex is involved in neuromuscular control during walking in human adults. Based on the difference in the neural control mechanisms of locomotion between rodent, human infants and adults, MU firing behavior during adult walking probably has some different features from the other populations. However, so far, the firing activity of MUs in human adult walking has been largely unknown due to technical issues. Approach. Recent technical advances allow noninvasive investigation of MU firing by high-density surface electromyogram (HDsEMG) decomposition. We investigated the MU firing behavior of the tibialis anterior (TA) muscle during walking at a slow speed by HDsEMG decomposition. Main results. We found recruitment threshold modulation of MU between walking and steady isometric contractions. Doublet firings, and gait phase-specific firings were also observed during walking. We also found high MU synchronization during walking over a wide range of frequencies, probably including cortical and spinal CPG-related components. The amount of MU synchronization was modulated between the gait phases and motor tasks. These results suggest that the central nervous system flexibly controls MU firing to generate appropriate force of TA during human walking. Significance. This study revealed the MU behavior during walking at a slow speed and demonstrated the feasibility of noninvasive investigation of MUs during dynamic locomotor tasks, which will open new frontiers for the study of neuromuscular systems in the fields of neuroscience and biomedical engineering.

Gait regulation using monopolar intraspinal micro-stimulation of spinal cord central pattern generator: New insights for improving Hodgkin–Huxley model

Restoring the motor function of paralyzed limbs has always been an important aim in the field of biomedical engineering. In view of the discovery of the repeatable experimental phenomenon that positive and negative stimulation pulses applied to specific points, identified as central pattern generator (CPG) sites, could induce switching of the movement patterns of bilateral hindlimbs, an improved Hodgkin–Huxley (HH) neuron model was established by introducing the electric field effect principle. A CPG neural network model comprising 12 neural units in six joints of the bilateral hindlimbs was modeled. The simulation results showed the alternating movement patterns of the bilateral hindlimbs through the action potential release of extensor and flexor neurons. The explosive electromyogram of the gastrocnemius (GM) and quadriceps femoris (QF) when stimulating the CPG sites with intraspinal micro-stimulation (ISMS) was consistent with the action potential diagram of the flexor and extensor neurons obtained via simulation. Our research considers the neural network model of electric field radiation, which can facilitate a deep understanding of the dynamic characteristics of neurons in the electric field environment, and verifies the correlation between the location of CPG sites, stimulus polarity and movement patterns to induce alternating left–right coordinated movements.

Treadmill Stepping after Epidural Stimulation Cessation in Decerebrated Cats

Summary: It was repeatedly shown that the locomotion evoked by epidural-induced electrical stimulation can last for a certain amount of time after stimulation cessation in decerebrated and spinal animals. This so-called after-stepping reflects the maintenance level for the activation of locomotor neuronal circuitry, but only scarce information exists about after-stepping peculiarities. We provide a comparative investigation of after-stepping and stepping under epidural stimulation using electromyographic and kinematic signals as well as ground reaction forces in 16 decerebrated cats. Our principal findings are as follows: (1) the ground reaction forces decrease more after epidural stimulation cessation compared to anterior–posterior limb movements; (2) the step cycle duration is longer for after-steps; (3) the electromyographic signal of the extensor gastrocnemius lateralis muscle during after-stepping decreases faster compared to the signal from the flexors iliopsoas and tibialis anterior and to the extensor soleus muscle; and (4) electromyographic stability is reduced after epidural stimulation cessation. We suppose that different levels of the spinal central pattern generator can be differently attenuated after external trigger cessation. These data could be important for the elaboration of locomotor models and for rehabilitation techniques. New Findings: Our new findings come from comparative investigations of the so-called after-stepping (locomotion after electrical stimulation cessation) and locomotion observed during epidural-induced electrical stimulation. Our new findings are as follows: after epidural stimulation cessation, (1) the ground reaction forces decrease faster compared to anterior–posterior limb movements; (2) the electromyographic signal of the extensor gastrocnemius lateralis muscle decreases faster compared to the signals from the flexors iliopsoas and tibialis anterior and to the extensor soleus muscle; and (3) electromyographic stability is reduced.

The effects of temperature changes on the mammalian spinal locomotor CPG network and the role of TRP channels in functional compensation

Preliminary data suggests that spinal cord neural networks that contain intact sensory pathways, which include dorsal root ganglia (DRG) and thermal transient receptor potential (TRP) channels are more resilient to gradual temperature changes than isolated preparations. Moreover, how acute temperature changes affect mammalian CPG‐driven motor activity remains uncertain. We studied how acute and gradual temperature changes impact the stability of motor networks with or without sensory pathways. More specifically, we aim to investigate: 1. the difference between how acute temperature changes versus gradual temperature changes can have an impact on the stability and robustness of motor networks; 2. how sensory inputs and TRP channels affect the adaptation of spinal central pattern generator (CPG) networks to changes in temperature. We compared changes in motor neuron bursting activity between ventral L2 and L5 roots of neonatal mouse spinal cord preparations under acute (from 20℃ directly to 29℃) and gradual (gradually from 20℃, to 23℃, to 26℃, and to 29℃) temperature change conditions. Spinal cord preparations both with and without DRGs were compared. We found that the locomotor activities were increased as temperature increase under both chronic and acute changes; however, spinal cord preparations without intact DRG showed activities with less stable phasing and more overall motor bursting variability compared to those preparations with intact DRGs (on L3, L4, and L5 spinal levels). Our results suggest that the lumbar spinal locomotor CPG network activity shows more susceptibility and less adaptation to temperature changes in the absence of sensory feedback provided by DRG sensory afferents. Further studies will be conducted in the presence of TRP channel blockers to preparations with DRGs to confirm the potential compensatory role that sensory feedback afferents convey to spinal CPG networks.

Emergence of Extreme Paw Accelerations During Cat Paw Shaking: Interactions of Spinal Central Pattern Generator, Hindlimb Mechanics and Muscle Length-Depended Feedback.

Cat paw shaking is a spinal reflex for removing an irritating stimulus from paw by developing extremely high paw accelerations. Previous studies of paw shaking revealed a proximal-to-distal gradient of hindlimb segmental velocities/accelerations, as well as complex inter-joint coordination: passive motion-dependent interaction moments acting on distal segments are opposed by distal muscle moments. However, mechanisms of developing extreme paw accelerations during paw shaking remain unknown. We hypothesized that paw-shaking mechanics and muscle activity might correspond to a whip-like mechanism of energy generation and transfer along the hindlimb. We first demonstrated in experiments with five intact, adult, female cats that during paw shaking, energy generated by proximal muscle moments was transmitted to distal segments by joint forces. This energy transfer was mostly responsible for the segmental velocity/acceleration proximal-to-distal gradient. Distal muscle moments mostly absorbed energy of the distal segments. We then developed a neuromechanical model of hindlimb paw shaking comprised a half-center CPG, activating hip flexors and extensors, and passive viscoelastic distal muscles that produced length/velocity-depended force. Simulations reproduced whip-like mechanisms found experimentally: the proximal-to-distal velocity/acceleration gradient, energy transfer by joint forces and energy absorption by distal muscle moments, as well as atypical co-activation of ankle and hip flexors with knee extensors. Manipulating model parameters, including reversal of segmental inertia distal-to-proximal gradient, demonstrated important inertia contribution to developing the segmental velocity/acceleration proximal-to-distal gradient. We concluded that extreme paw accelerations during paw shaking result from interactions between a spinal CPG, hindlimb segmental inertia, and muscle length/velocity-depended feedback that tunes limb viscoelastic properties.

What Is the Brainstem Control of Locomotion?

Locomotion in humans is defined as bipedal progression through stages of a gait cycle to move from one place to another while maintaining balance and posture. Locomotion can be categorized in temporal phases (initiation, actual locomotive episode/execution, and termination) or in behavioral categories (slow exploratory and fast speed locomotion). The motivation behind a locomotive episode may be driven by internal needs (goal driven from the motor cortex or emotion driven from the limbic system) or external environmental cues. Locomotion is mediated by a spinal central pattern generator (CPG) under the influence of the brainstem reticular formation and is integrated with control of muscle tone and posture. Control of gait, muscle tone, and posture involves complex interactions among the sensorimotor cortex, basal ganglia, basal forebrain, cerebellum, brainstem, and spinal cord.1-3 Pioneering studies in cats4 and monkeys5,6 and more recently in rodents7-12 have contributed to elucidate the brainstem mechanisms controlling locomotion. This information, together with indirect evidence from human electrophysiologic and functional neuroimaging studies, provides testable pathophysiologic hypotheses and potential therapeutic targets for gait control disorders. The focus of this review is on brainstem mechanisms controlling locomotion. The role of other CNS areas in control of gait and posture and their abnormalities in disorders such as Parkinson disease (PD) have been extensively reviewed1 and are only briefly discussed here.

An injury-induced serotonergic neuron subpopulation contributes to axon regrowth and function restoration after spinal cord injury in zebrafish

Spinal cord injury (SCI) interrupts long-projecting descending spinal neurons and disrupts the spinal central pattern generator (CPG) that controls locomotion. The intrinsic mechanisms underlying re-wiring of spinal neural circuits and recovery of locomotion after SCI are unclear. Zebrafish shows axonal regeneration and functional recovery after SCI making it a robust model to study mechanisms of regeneration. Here, we use a two-cut SCI model to investigate whether recovery of locomotion can occur independently of supraspinal connections. Using this injury model, we show that injury induces the localization of a specialized group of intraspinal serotonergic neurons (ISNs), with distinctive molecular and cellular properties, at the injury site. This subpopulation of ISNs have hyperactive terminal varicosities constantly releasing serotonin activating 5-HT1B receptors, resulting in axonal regrowth of spinal interneurons. Axon regrowth of excitatory interneurons is more pronounced compared to inhibitory interneurons. Knock-out of htr1b prevents axon regrowth of spinal excitatory interneurons, negatively affecting coordination of rostral-caudal body movements and restoration of locomotor function. On the other hand, treatment with 5-HT1B receptor agonizts promotes functional recovery following SCI. In summary, our data show an intraspinal mechanism where a subpopulation of ISNs stimulates axonal regrowth resulting in improved recovery of locomotor functions following SCI in zebrafish.

Semaphorin7A: its role in the control of serotonergic circuits and functional recovery following spinal cord injury.

Serotonin is a monoamine neurotransmitter synthetized in various populations of brainstem neurons. In the spinal cord, descending serotonergic projections regulate postural muscle tone, locomotion and rhythm and coordination of movements via the Central Pattern Generator. Following a spinal cord injury, serotonergic projections to the lumbar spinal cord, where the Central Pattern Generators are located, are interrupted resulting in devastating locomotor impairments and changes in the expression and activation of serotonin and its spinal receptors. The molecular cues that control the precise patterning and targeting of serotonergic inputs onto Central Pattern Generator networks in healthy animals or after injury are still unknown. In our recent research work, we have been particularly interested in Semaphorin7A, which belongs to the Semaphorins family involved in guiding growing axons and controlling plasticity of synaptic connections. In this review, we discuss the role of Semaphorin7A signaling as an important molecular actor that instructs the patterning of serotonin inputs to spinal Central Pattern Generator networks. We show that Semaphorin7A controls the wiring of descending serotonin axons in the spinal cord. Our results reveal that mistargetting of serotonin fibers in the spinal cord is compensated in healthy uninjured Semaphorin7A deficient mice so that their gross locomotion proceeds accurately. We also demonstrate that when the system is challenged with a spinal lesion, the pattern of post-injury serotonin expression is significantly altered in Semaphorin7A deficient mice with specific ectopic targeting of serotonin fibers in the lumbar spinal cord. Compensatory mechanisms in place in uninjured Semaphorin7A deficient mice are lost and injured Semaphorin7A deficient mice exhibit a worsening of their post-injury locomotor abilities. Our findings identify Semaphorin7A as a critical determinant of serotonergic circuit formation in healthy or spinal cord injured mice.

Inhibition and Facilitation of the Spinal Locomotor Central Pattern Generator and Reflex Circuits by Somatosensory Feedback From the Lumbar and Perineal Regions After Spinal Cord Injury.

Somatosensory feedback from peripheral receptors dynamically interacts with networks located in the spinal cord and brain to control mammalian locomotion. Although somatosensory feedback from the limbs plays a major role in regulating locomotor output, those from other regions, such as lumbar and perineal areas also shape locomotor activity. In mammals with a complete spinal cord injury, inputs from the lumbar region powerfully inhibit hindlimb locomotion, while those from the perineal region facilitate it. Our recent work in cats with a complete spinal cord injury shows that they also have opposite effects on cutaneous reflexes from the foot. Lumbar inputs increase the gain of reflexes while those from the perineal region decrease it. The purpose of this review is to discuss how somatosensory feedback from the lumbar and perineal regions modulate the spinal locomotor central pattern generator and reflex circuits after spinal cord injury and the possible mechanisms involved. We also discuss how spinal cord injury can lead to a loss of functional specificity through the abnormal activation of functions by somatosensory feedback, such as the concurrent activation of locomotion and micturition. Lastly, we discuss the potential functions of somatosensory feedback from the lumbar and perineal regions and their potential for promoting motor recovery after spinal cord injury.

Induction of Ventral Spinal V0 Interneurons from Mouse Embryonic Stem Cells.

The ventral spinal population of V0 interneurons (INs) contributes to the coordinated movements directed by spinal central pattern generators (CPGs), including respiratory circuits and left-right alternation in locomotion. One challenge in studying V0 INs has been the limited number of cells that can be isolated from primary sources for basic research or therapeutic use. However, derivation from a pluripotent source, such as has been done recently for other IN populations, could resolve this issue. However, there is currently no protocol to specifically derive V0 interneurons from pluripotent cell types. To generate an induction protocol, mouse embryonic stem cells (mESCs) were grown in suspension culture and then exposed to retinoic acid (RA) and collected at different time points to measure mRNA expression of the V0 progenitor transcription factor marker, Dbx1, and postmitotic transcription factor marker, Evx1. The cultures were also exposed to the sonic hedgehog signaling pathway agonist purmorphamine (purm) and the Notch signaling pathway inhibitor N-{N-(3,5-difluorophenacetyl-L-alanyl)}-(S)-phenylglycine-t-butyl-ester (DAPT) to determine if either of these pathways contribute to V0 IN induction, specifically the ventral (V0V) subpopulation. From the various parameters tested, the final protocol that generated the greatest percentage of cells expressing V0V IN markers was an 8-day protocol using 4 days of suspension culture to form embryoid bodies followed by addition of 1 μM RA from days 4 to 8, 100 nM purm from days 4 to 6, and 5 μM DAPT from days 6 to 8. This protocol will allow investigators to obtain V0 IN cultures for use in in vitro studies, such as those examining CPG microcircuits, electrophysiological characterization, or even for transplantation studies in injury or disease models.

Reproducing Five Motor Behaviors in a Salamander Robot With Virtual Muscles and a Distributed CPG Controller Regulated by Drive Signals and Proprioceptive Feedback.

Diverse locomotor behaviors emerge from the interactions between the spinal central pattern generator (CPG), descending brain signals and sensory feedback. Salamander motor behaviors include swimming, struggling, forward underwater stepping, and forward and backward terrestrial stepping. Electromyographic and kinematic recordings of the trunk show that each of these five behaviors is characterized by specific patterns of muscle activation and body curvature. Electrophysiological recordings in isolated spinal cords show even more diverse patterns of activity. Using numerical modeling and robotics, we explored the mechanisms through which descending brain signals and proprioceptive feedback could take advantage of the flexibility of the spinal CPG to generate different motor patterns. Adapting a previous CPG model based on abstract oscillators, we propose a model that reproduces the features of spinal cord recordings: the diversity of motor patterns, the correlation between phase lags and cycle frequencies, and the spontaneous switches between slow and fast rhythms. The five salamander behaviors were reproduced by connecting the CPG model to a mechanical simulation of the salamander with virtual muscles and local proprioceptive feedback. The main results were validated on a robot. A distributed controller was used to obtain the fast control loops necessary for implementing the virtual muscles. The distributed control is demonstrated in an experiment where the robot splits into multiple functional parts. The five salamander behaviors were emulated by regulating the CPG with two descending drives. Reproducing the kinematics of backward stepping and struggling however required stronger muscle contractions. The passive oscillations observed in the salamander's tail during forward underwater stepping could be reproduced using a third descending drive of zero to the tail oscillators. This reduced the drag on the body in our hydrodynamic simulation. We explored the effect of local proprioceptive feedback during swimming and forward terrestrial stepping. We found that feedback could replace or reduce the need for different drives in both cases. It also reduced the variability of intersegmental phase lags toward values appropriate for locomotion. Our work suggests that different motor behaviors do not require different CPG circuits: a single circuit can produce various behaviors when modulated by descending drive and sensory feedback.

Emergence of functional neuromuscular junctions in an engineered, multicellular spinal cord-muscle bioactuator.

Three-dimensional (3D) biomimetic systems hold great promise for the study of biological systems in vitro as well as for the development and testing of pharmaceuticals. Here, we test the hypothesis that an intact segment of lumbar rat spinal cord will form functional neuromuscular junctions (NMJs) with engineered, 3D muscle tissue, mimicking the partial development of the peripheral nervous system (PNS). Muscle tissues are grown on a 3D-printed polyethylene glycol (PEG) skeleton where deflection of the backbone due to muscle contraction causes the displacement of the pillar-like “feet.” We show that spinal cord explants extend a robust and complex arbor of motor neurons and glia in vitro. We then engineered a “spinobot” by innervating the muscle tissue with an intact segment of lumbar spinal cord that houses the hindlimb locomotor central pattern generator (CPG). Within 7 days of the spinal cord being introduced to the muscle tissue, functional neuromuscular junctions (NMJs) are formed, resulting in the development of an early PNS in vitro. The newly innervated muscles exhibit spontaneous contractions as measured by the displacement of pillars on the PEG skeleton. Upon chemical excitation, the spinal cord-muscle system initiated muscular twitches with a consistent frequency pattern. These sequences of contraction/relaxation suggest the action of a spinal CPG. Chemical inhibition with a blocker of neuronal glutamate receptors effectively blocked contractions. Overall, these data demonstrate that a rat spinal cord is capable of forming functional neuromuscular junctions ex vivo with an engineered muscle tissue at an ontogenetically similar timescale.

Towards an Understanding of Control of Complex Rhythmical "Wavelike" Coordination in Humans.

How does the human neurophysiological system self-organize to achieve optimal phase relationships among joints and limbs, such as in the composite rhythms of butterfly and front crawl swimming, drumming, or dancing? We conducted a systematic review of literature relating to central nervous system (CNS) control of phase among joint/limbs in continuous rhythmic activities. SCOPUS and Web of Science were searched using keywords “Phase AND Rhythm AND Coordination”. This yielded 1039 matches from which 23 papers were extracted for inclusion based on screening criteria. The empirical evidence arising from in-vivo, fictive, in-vitro, and modelling of neural control in humans, other species, and robots indicates that the control of movement is facilitated and simplified by innervating muscle synergies by way of spinal central pattern generators (CPGs). These typically behave like oscillators enabling stable repetition across cycles of movements. This approach provides a foundation to guide the design of empirical research in human swimming and other limb independent activities. For example, future research could be conducted to explore whether the Saltiel two-layer CPG model to explain locomotion in cats might also explain the complex relationships among the cyclical motions in human swimming.

The Hemodynamic Mass Action of a Central Pattern Generator.

The hemodynamic response is a neurovascular and metabolic process in which there is rapid delivery of blood flow to a neuronal tissue in response to neuronal activation. The functional magnetic resonance imaging (fMRI) and the functional near-infrared spectroscopy (fNIRS), for instance, are based on the physiological principles of such hemodynamic responses. Both techniques allow the mapping of active neuronal regions in which the neurovascular and metabolic events are occurring. However, although both techniques have revolutionized the neurosciences, they are mostly employed for neuroimaging of the human brain but not for the spinal cord during functional tasks. Moreover, little is known about other techniques measuring the hemodynamic response in the spinal cord. The purpose of the present study was to show for the first time that a simple optical system termed direct current photoplethysmography (DC-PPG) can be employed to detect hemodynamic responses of the spinal cord and the brainstem during the functional activation of the spinal central pattern generator (CPG). In particular, we positioned two DC-PPG systems directly on the brainstem and spinal cord during fictive scratching in the cat. The optical DC-PPG systems allowed the trial-by-trial recording of massive hemodynamic signals. We found that the “strength” of the flexor-plus-extensor motoneuron activities during motor episodes of fictive scratching was significantly correlated to the “strengths” of the brainstem and spinal DC-PPG signals. Because the DC-PPG was robustly detected in real-time, we claim that such a functional signal reflects the hemodynamic mass action of the brainstem and spinal cord associated with the CPG motor action. Our findings shed light on an unexplored hemodynamic observable of the spinal CPGs, providing a proof of concept that the DC-PPG can be used for the assessment of the integrity of the human CPGs.

Multiple Rhythm-Generating Circuits Act in Tandem with Pacemaker Properties to Control the Start and Speed of Locomotion

In vertebrates, specific command centers in the brain can selectively drive slow-explorative or fast-speed locomotion. However, it remains unclear how the locomotor central pattern generator (CPG) processes descending drive into coordinated locomotion. Here, we reveal, in adult zebrafish, a logic of the V2a interneuron rhythm-generating circuits involving recurrent and hierarchical connectivity that acts in tandem with pacemaker properties to provide an ignition and gear-shift mechanism to start locomotion and change speed. A comprehensive mapping of synaptic connections reveals three recurrent circuit modules engaged sequentially to increase locomotor speed. The connectivity between V2a interneurons of different modules displayed a clear asymmetry in favor of connections from faster to slower modules. The interplay between V2a interneuron pacemaker properties and their organized connectivity provides a mechanism for locomotor initiation and speed control. Thus, our results provide mechanistic insights into how the spinal CPG transforms descending drive into locomotion and align its speed with the initial intention.

Gait Generation and Its Energy Efficiency Based on Rat Neuromusculoskeletal Model.

Changing gait is crucial for adaptive and smooth animal locomotion. Although it remains unclear what makes animals decide on a specific gait, energy efficiency is an important factor. It has been reported that the relationship of oxygen consumption with speed is U-shaped for each horse gait and that different gaits have different speeds at which oxygen consumption is minimized. This allows the horse to produce energy-efficient locomotion in a wide speed range by changing gait. However, the underlying mechanisms causing oxygen consumption to be U-shaped and the speeds for the minimum consumption to be different between different gaits are unclear. In the present study, we used a neuromusculoskeletal model of the rat to examine the mechanism from a dynamic viewpoint. Specifically, we constructed the musculoskeletal part of the model based on empirical anatomical data on rats and the motor control model based on the physiological concepts of the spinal central pattern generator and muscle synergy. We also incorporated the posture and speed regulation models at the levels of the brainstem and cerebellum. Our model achieved walking through forward dynamic simulation, and the simulated joint kinematics and muscle activities were compared with animal data. Our model also achieved trotting by changing only the phase difference of the muscle-synergy-based motor commands between the forelimb and hindlimb. Furthermore, the speed of each gait varied by changing only the extension phase duration and amplitude of the muscle synergy-based motor commands and the reference values for the regulation models. The relationship between cost of transport (CoT) and speed was U-shaped for both the generated walking and trotting, and the speeds for the minimum CoT were different for the two gaits, as observed in the oxygen consumption of horses. We found that the resonance property and the posture and speed regulations contributed to the CoT shape and difference in speeds for the minimum CoT. We further discussed the energy efficiency of gait based on the simulation results.