Single Central Pattern Generator Research Articles

Central pattern generator network model for the alternating hind limb gait of rats based on the modified Van der Pol equation.

Herein, we employed a central pattern generator (CPG), a spinal cord neural network that regulates lower-limb gait during intra-spinal micro-stimulation (ISMS). Particularly, ISMS was used to determine the spatial distribution pattern of CPG sites in the spinal cord and the signal regulation pattern that induced the CPG network to produce coordinated actions. Based on the oscillation phenomenon of the single CPG neurons of Van der Pol (VDP) oscillators, a double-cell CPG neural network model was constructed to realise double lower limbs, six-joint modelling, the simulation of 12 neural circuits, the CPG loci characterising stimuli-inducing alternating movements and changes in polarity stimulation signals in rat hindlimbs, and leg-state change movements. The feasibility and effectiveness of the CPG neural network were verified by recording the electromyographic burst-release mode of the flexor and extensor muscles of the knee joints during CPG electrical stimulation. The results revealed that the output pattern of the CPG presented stable rhythm and coordination characteristics. The 12-neuron CPG model based on the improved VDP equation realised single-point control while significantly reducing the number of stimulation electrodes in the gait training of spinal cord injury patients. We believe that this study advances motor function recovery in rehabilitation medicine.

Contributions of h- and Na+/K+ Pump Currents to the Generation of Episodic and Continuous Rhythmic Activities.

Developing spinal motor networks produce a diverse array of outputs, including episodic and continuous patterns of rhythmic activity. Variation in excitability state and neuromodulatory tone can facilitate transitions between episodic and continuous rhythms; however, the intrinsic mechanisms that govern these rhythms and their transitions are poorly understood. Here, we tested the capacity of a single central pattern generator (CPG) circuit with tunable properties to generate multiple outputs. To address this, we deployed a computational model composed of an inhibitory half-center oscillator (HCO). Following predictions of our computational model, we tested the contributions of key properties to the generation of an episodic rhythm produced by isolated spinal cords of the newborn mouse. The model recapitulates the diverse state-dependent rhythms evoked by dopamine. In the model, episodic bursting depended predominantly on the endogenous oscillatory properties of neurons, with Na+/K+ ATPase pump (IPump) and hyperpolarization-activated currents (Ih) playing key roles. Modulation of either IPump or Ih produced transitions between episodic and continuous rhythms and silence. As maximal activity of IPump decreased, the interepisode interval and period increased along with a reduction in episode duration. Decreasing maximal conductance of Ih decreased episode duration and increased interepisode interval. Pharmacological manipulations of Ih with ivabradine, and IPump with ouabain or monensin in isolated spinal cords produced findings consistent with the model. Our modeling and experimental results highlight key roles of Ih and IPump in producing episodic rhythms and provide insight into mechanisms that permit a single CPG to produce multiple patterns of rhythmicity.

Patterns of Whisker Movement Activity in the States of Sleep and Waking in Neonatal Rats

The aims of the present work was to describe primitive whisker movements in neonatal Wistar rats (postnatal days 4–7) in the states of sleep and waking and to study correlations between whisker movements and body movements. Whisker movements were recorded by high-speed video recording and the animals’ behavioral state was determined by recording electromyographic activity of the cervical muscles and simultaneous recording of limb movements using piezo elements. During active sleep, movements consisted mostly of short-term whisker movements, and a significant proportion of these movements arose simultaneously with short-term bursts of activity in the cervical muscles and transient myoclonic twitches of the animal’s body. During periods of waking, movements were mostly complex long-lasting whisker movements, which were accompanied by long-term increases in cervical muscle tone and complex body and limb movements. Both types of whisker movement occurred mainly in the rostral and caudal directions, and the amplitude of movements during waking was only slightly greater than the amplitude of whisker movements during sleep. The data obtained here provide evidence that the temporal organization of whisker movement activity in neonatal rats is significantly different in the states of sleep and waking and that whisker movements in both behavioral states showed strong correlations with the animal’s body movements. It is suggested that generalized primitive whisker and body movements in neonatal rats are due to the activity of a single central pattern generator both in the state of active sleep and in the state of waking.

Control of transitions between locomotor-like and paw shake-like rhythms in a model of a multistable central pattern generator.

The ability of the same neuronal circuit to control different motor functions is an actively debated concept. Previously, we showed in a model that a single multistable central pattern generator (CPG) could produce two different rhythmic motor patterns, slow and fast, corresponding to cat locomotion and paw shaking. A locomotor-like rhythm (~1 Hz) and a paw shake-like rhythm (~10 Hz) did coexist in our model, and, by applying a single pulse of current, we could switch the CPG from one regime to another (Bondy B, Klishko AN, Edwards DH, Prilutsky BI, Cymbalyuk G. In: Neuromechanical Modeling of Posture and Locomotion, 2016). Here we investigated the roles of slow intrinsic ionic currents in this multistability. The CPG is modeled as a half-center oscillator circuit comprising two reciprocally inhibitory neurons. Each neuron is equipped with two slow inward currents, a Na+ current ( INaS) and a Ca2+ current ( ICaS). ICaS inactivates much more slowly and at more hyperpolarized voltages than INaS. We demonstrate that INaS is the primary current driving the paw shake-like bursting. ICaS is crucial for the locomotor-like bursting, and it is inactivated during the paw shake-like activity. We investigate the sensitivity of the bursting regimes to perturbations, using a pulse of current to induce a switch from one regime to the other, and we demonstrate that the transition duration is dependent on pulse amplitude and application phase. We also investigate the modulatory roles of the strength of various currents on characteristics of these rhythms and show that their effects are regime specific. We conclude that a multistable CPG is physiologically plausible and derive testable predictions of the model. NEW & NOTEWORTHY Little is known about how a single central pattern generator could produce multiple rhythms. We describe a novel mechanism for multistability of bursting regimes with strongly distinct periods. The proposed mechanism emphasizes the role of intrinsic cellular dynamics over synaptic dynamics in the production of multistability. We describe how the temporal characteristics of multiple rhythms could be controlled by neuromodulation and how single pulses of current could produce a switch between regimes in a functional fashion.

Multifunctional central pattern generator controlling walking and paw shaking

Central pattern generators (CPGs) are oscillatory neuronal networks controlling rhythmic motor tasks such as breathing and walking. A multifunctional CPG can produce multiple patterns, e.g. patterns with different periods [1-5]. Here, we investigate whether a pair of cat behaviors -- walking and paw shaking -- could be controlled by a single multifunctional CPG exhibiting multistability of oscillatory regimes. In experiments, both behaviors can be elicited in a spinalized cat, and there is evidence that the same circuitry is used for both rhythms [2,3]. We present a parsimonious model of a half-center oscillator composed of two mutually inhibitory neurons. These cells contains two slowly inactivating inward currents, a persistent Na+ current (INaP) and a low voltage activated Ca++ current (ICaLVA). The dynamics of the multifunctional CPG is based on that the ICaLVA inactivates much slower than INaP and at the more hyperpolarized membrane potentials. Here, we demonstrate the co-existence of two rhythms (Figure ​(Figure1).1). At first, the model demonstrates walking pattern. A switch from a slow, 1-2 Hz walking rhythm to fast, 7-10 Hz paw shake rhythm was elicited by a pulse of conductance of excitatory current delivered to extensor and flexor neurons. Then, a switch back to walking was triggered by a shorter pulse of conductance of inhibitory current delivered to the extensor neuron. Figure 1 Two mutually inhibitory interneurons, IntE (Extensor Interneuron) and IntF (Flexor Interneuron) produce alternating bursting activity at approximately 1.6 Hz representing walking pattern. A switch to paw shaking is executed by a pulse of excitatory conductance ... The CPG model was also incorporated into a neuromechanical model of a cat hindlimb in the AnimatLab environment [6]. The model provides a cellular mechanism of multifunctional CPG operation.

Multiple chaotic central pattern generators with learning for legged locomotion and malfunction compensation

An originally chaotic system can be controlled into various periodic dynamics. When it is implemented into a legged robot’s locomotion control as a central pattern generator (CPG), sophisticated gait patterns arise so that the robot can perform various walking behaviors. However, such a single chaotic CPG controller has difficulties dealing with leg malfunction. Specifically, in the scenarios presented here, its movement permanently deviates from the desired trajectory. To address this problem, we extend the single chaotic CPG to multiple CPGs with learning. The learning mechanism is based on a simulated annealing algorithm. In a normal situation, the CPGs synchronize and their dynamics are identical. With leg malfunction or disability, the CPGs lose synchronization leading to independent dynamics. In this case, the learning mechanism is applied to automatically adjust the remaining legs’ oscillation frequencies so that the robot adapts its locomotion to deal with the malfunction. As a consequence, the trajectory produced by the multiple chaotic CPGs resembles the original trajectory far better than the one produced by only a single CPG. The performance of the system is evaluated first in a physical simulation of a quadruped as well as a hexapod robot and finally in a real six-legged walking machine called AMOSII. The experimental results presented here reveal that using multiple CPGs with learning is an effective approach for adaptive locomotion generation where, for instance, different body parts have to perform independent movements for malfunction compensation.

Coordination of Distinct Motor Structures through Remote Axonal Coupling of Projection Interneurons

Complex behaviors often require coordinated movements of dissimilar motor structures. The underlying neural mechanisms are poorly understood. We investigated cycle-by-cycle coordination of two dissimilar feeding structures in Aplysia californica: the external lips and the internal radula. During feeding, the lips open while the radula protracts. Lip and radula motoneurons are located in the cerebral and buccal ganglia, respectively, and radula motoneurons are controlled by a well characterized buccal central pattern generator (CPG). Here, we examined whether the three electrically coupled lip motoneurons C15/16/17 are controlled by the buccal CPG or by a previously postulated cerebral CPG. Two buccal-cerebral projection interneurons, B34 and B63, which are part of the buccal CPG and mediate radula protraction, monosynaptically excite C15/16/17. Recordings from the B34 axon in the cerebral ganglion demonstrate its direct electrical coupling with C15/16/17, eliminating the need for a cerebral CPG. Moreover, when the multifunctional buccal CPG generates multiple forms of motor programs due to the activation of two inputs, the command-like neuron CBI-2 and the esophageal nerve (EN), C15/16 exhibit activity patterns that are distinct from C17. These distinct activity patterns result from combined activity of B34 and B63 and their differential excitation of C15/16 versus C17. In more general terms, we identified neuronal mechanisms that allow a single CPG to coordinate the phasing and activity of remotely located motoneurons innervating distinct structures that participate in the production of different motor outputs. We also demonstrated that axodendritic electrical coupling by projection interneurons plays a pivotal role in coordinating activity of these remotely located neurons.

Partly Shared Spinal Cord Networks for Locomotion and Scratching

Animals produce a variety of behaviors using a limited number of muscles and motor neurons. Rhythmic behaviors are often generated in basic form by networks of neurons within the central nervous system, or central pattern generators (CPGs). It is known from several invertebrates that different rhythmic behaviors involving the same muscles and motor neurons can be generated by a single CPG, multiple separate CPGs, or partly overlapping CPGs. Much less is known about how vertebrates generate multiple, rhythmic behaviors involving the same muscles. The spinal cord of limbed vertebrates contains CPGs for locomotion and multiple forms of scratching. We investigated the extent of sharing of CPGs for hind limb locomotion and for scratching. We used the spinal cord of adult red-eared turtles. Animals were immobilized to remove movement-related sensory feedback and were spinally transected to remove input from the brain. We took two approaches. First, we monitored individual spinal cord interneurons (i.e., neurons that are in between sensory neurons and motor neurons) during generation of each kind of rhythmic output of motor neurons (i.e., each motor pattern). Many spinal cord interneurons were rhythmically activated during the motor patterns for forward swimming and all three forms of scratching. Some of these scratch/swim interneurons had physiological and morphological properties consistent with their playing a role in the generation of motor patterns for all of these rhythmic behaviors. Other spinal cord interneurons, however, were rhythmically activated during scratching motor patterns but inhibited during swimming motor patterns. Thus, locomotion and scratching may be generated by partly shared spinal cord CPGs. Second, we delivered swim-evoking and scratch-evoking stimuli simultaneously and monitored the resulting motor patterns. Simultaneous stimulation could cause interactions of scratch inputs with subthreshold swim inputs to produce normal swimming, acceleration of the swimming rhythm, scratch-swim hybrid cycles, or complete cessation of the rhythm. The type of effect obtained depended on the level of swim-evoking stimulation. These effects suggest that swim-evoking and scratch-evoking inputs can interact strongly in the spinal cord to modify the rhythm and pattern of motor output. Collectively, the single-neuron recordings and the results of simultaneous stimulation suggest that important elements of the generation of rhythms and patterns are shared between locomotion and scratching in limbed vertebrates.

Computer simulations of neural mechanisms explaining upper and lower limb excitatory neural coupling

BackgroundWhen humans perform rhythmic upper and lower limb locomotor-like movements, there is an excitatory effect of upper limb exertion on lower limb muscle recruitment. To investigate potential neural mechanisms for this behavioral observation, we developed computer simulations modeling interlimb neural pathways among central pattern generators. We hypothesized that enhancement of muscle recruitment from interlimb spinal mechanisms was not sufficient to explain muscle enhancement levels observed in experimental data.MethodsWe used Matsuoka oscillators for the central pattern generators (CPG) and determined parameters that enhanced amplitudes of rhythmic steady state bursts. Potential mechanisms for output enhancement were excitatory and inhibitory sensory feedback gains, excitatory and inhibitory interlimb coupling gains, and coupling geometry. We first simulated the simplest case, a single CPG, and then expanded the model to have two CPGs and lastly four CPGs. In the two and four CPG models, the lower limb CPGs did not receive supraspinal input such that the only mechanisms available for enhancing output were interlimb coupling gains and sensory feedback gains.ResultsIn a two-CPG model with inhibitory sensory feedback gains, only excitatory gains of ipsilateral flexor-extensor/extensor-flexor coupling produced reciprocal upper-lower limb bursts and enhanced output up to 26%. In a two-CPG model with excitatory sensory feedback gains, excitatory gains of contralateral flexor-flexor/extensor-extensor coupling produced reciprocal upper-lower limb bursts and enhanced output up to 100%. However, within a given excitatory sensory feedback gain, enhancement due to excitatory interlimb gains could only reach levels up to 20%. Interconnecting four CPGs to have ipsilateral flexor-extensor/extensor-flexor coupling, contralateral flexor-flexor/extensor-extensor coupling, and bilateral flexor-extensor/extensor-flexor coupling could enhance motor output up to 32%. Enhancement observed in experimental data exceeded 32%. Enhancement within this symmetrical four-CPG neural architecture was more sensitive to relatively small interlimb coupling gains. Excitatory sensory feedback gains could produce greater output amplitudes, but larger gains were required for entrainment compared to inhibitory sensory feedback gains.ConclusionsBased on these simulations, symmetrical interlimb coupling can account for much, but not all of the excitatory neural coupling between upper and lower limbs during rhythmic locomotor-like movements.

A Multi-rhythmic Oscillator Model that Can Integrate Motion Stabilization with Motion Exploration

Central pattern generators (CPGs) have been increasingly attracting roboticists in the hope that they enable robots to realize truly supple and agile locomotion under real world constraints. Thus far, various CPG models have been proposed, particularly in terms of motion stabilization against external perturbations, i.e., limit cycle behavior. On the other hand, biological CPGs have another crucial aspect that cannot be neglected, i.e., motion exploration. Here, note that motion stabilization and motion exploration should be performed in different time-scales. Now the following questions arise: how can different time-scales be embedded into a single CPG effectively?; and what is a good mathematical tool for describing the coexistence of different time-scales? To overcome these problems, this paper introduces a novel oscillator model in which the two functions of motion stabilization and motion exploration can be seamlessly integrated by exploiting the concept of multi-rhythmicity, without relying on any hierarchical structure, which in turn enables that learning is an integral part of the motor control system. We applied this model to the learning of hopping motion as a practical example. Simulation results indicate that the robot can successfully perform online learning without the need for a separation between learning and performance phases.

The Beat Goes On, and Up and Down.Focus on “Bursts of Information: Coordinating Interneurons Encode Multiple Parameters of a Periodic Motor Pattern”

The effective production of many motor behaviors requires the strict coordination of discrete motor pattern generating circuits ([Hill et al. 2003][1]). Locomotor behaviors usually require this coordination at several levels of the nervous system, within single limbs (interjoint coordination),

G protein signaling in a neuronal network is necessary for rhythmic motor pattern production.

G protein-coupled receptors are widely recognized as playing important roles in mediating the actions of extrinsic neuromodulatory inputs to motor networks. However, the potential for their direct involvement in rhythmic motor pattern generation has received considerably less attention. Results from this study indicate that G protein signaling appears to be integral to the operation of the central pattern generator (CPG) underlying the escape swim of the mollusk Tritonia diomedea. Blocking G protein signaling in a single CPG neuron, cerebral neuron C2, with intracellular iontophoresis of the guanine nucleotide analogue guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S), prevented the production of the swim motor program. Moreover, tonic activation of G protein signaling in this neuron by iontophoresis of the GTP analogues guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) and 5'-guanylyl-imidodiphosphate also inhibited motor pattern production. The possible sites of action of these guanine nucleotide analogues were examined to assess potential mechanisms by which they interfered with motor pattern production. Intracellular iontophoresis of GDP-beta-S into C2 did not affect C2 basal synaptic strength. However, it did reduce heterosynaptic facilitation of C2 synapses caused by the dorsal swim interneurons (DSIs), a set of serotonergic swim CPG neurons. In contrast, GTP-gamma-S directly enhanced C2 synaptic strength onto DFN, mimicking the neuromodulatory effect of the DSIs. GDP-beta-S, but not the GTP analogues, decreased C2 excitability, whereas both GTP analogues, but not GDP-beta-S, blocked the ability of DSI stimulation to increase C2 excitability. The decrease in C2 excitability caused by GDP-beta-S is not likely to be responsible for the inhibition of the swim motor pattern because decreasing C2 firing rate, by injecting hyperpolarizing current, did not prevent the production of the rhythmic motor pattern. Taken together, these data suggest that G protein signaling is a necessary and integral component of the escape swim CPG in Tritonia and that G protein signaling mediates DSI heterosynaptic facilitation of C2 but may not mediate the DSI-evoked enhancement of C2 excitability.

Loss of Self-Inhibition Is a Cellular Mechanism for Episodic Rhythmic Behavior

Background: Rhythmic motor behaviors can be generated continuously (e.g., breathing) or episodically (e.g., locomotion, swallowing), when short or long bouts of rhythmic activity are interspersed with periods of quiescence. Although the mechanisms of rhythm generation are known in detail in many systems, there is very little understanding of how the episodic nature of rhythmic behavior is produced at the neuronal level.Results: Using a well-established episodic rhythm-generating neural circuit controlling molluscan feeding, we demonstrate that quiescence between bouts of activity arises from active, maintained inhibition of an otherwise rhythmically active network. We show that the source of the suppressive drive is within the circuit itself; a single central pattern generator (CPG) interneuron type that fires tonically to inhibit feeding during quiescence. Suppression of the tonic activity of this neuron by food is sufficient to change the network from an inactive to a rhythmically active state, with the cell switching function to fire phasically as part of the food-evoked rhythmogenesis. Furthermore, the absolute level of intrinsic suppressive control is modulated extrinsically by the animal's behavioral state (e.g., hunger/satiety), increasing the probability of episodes of feeding when the animal is hungry.Conclusions: By utilizing the same intrinsic member of a CPG network in both rhythm-generation and suppression, this system has developed a simple and efficient mechanism for generating a variable level of response to suit the animal's changing behavioral demands.

Interneuronal and peptidergic control of motor pattern switching in Aplysia.

It has been proposed that a choice of specific behaviors can be mediated either by activation of behavior-specific higher order neurons or by distinct combinations of such neurons in different behaviors. We examined the role that two higher order neurons, CBI-2 and CBI-3, play in the selection of motor programs that correspond to ingestion and egestion, two stimulus-dependent behaviors that are generated by a single central pattern generator (CPG) of Aplysia. We found that CBI-2 could evoke either ingestive, egestive, or ambiguous motor programs depending on the regime of stimulation. When CBI-2 recruited CBI-3 firing via electrical coupling, the motor program tended to be ingestive. In the absence of CBI-3 activation, the program was usually egestive. When CBI-2 was stimulated to produce ingestive programs, hyperpolarization of CBI-3 converted the programs to egestive or ambiguous. When CBI-2 was stimulated to produce egestive or ambiguous programs, co-stimulation of CBI-3 converted them into ingestive. These findings are consistent with the idea that combinatorial commands are responsible for the choice of specific behaviors. Additional support for this view comes from the observations that appropriate stimulus conditions exist both for activation of CBI-2 together with CBI-3, and for activation of CBI-2 without a concomitant activation of CBI-3. The ability of CBI-3 to convert egestive and ambiguous programs into ingestive ones was mimicked by application of APGWamide, a neuropeptide that we have detected in CBI-3 by immunostaining. Thus combinatorial actions of higher order neurons that underlie pattern selection may involve the use of modulators released by specific higher order neurons.

Neural control of interlimb oscillations

Behavioral data concerning animal and human gaits and gait transitions are simulated as emergent properties of a central pattern generator (CPG) model. The CPG model is a version of the Ellias-Grossberg oscillator. Its neurons obey Hodgkin-Huxley type equations whose excitatory signals operate on a faster time scale than their inhibitory signals in a recurrent on-center off-surround anatomy. A descending command or GO signal activates the gaits and triggers gait transitions as its amplitude increases. A single model CPG can generate both in-phase and anti-phase oscillations at different GO amplitudes. Phase transitions from either in-phase to anti-phase oscillations or from anti-phase to in-phase oscillations can occur in different parameter ranges, as the GO signal increases. Quadruped vertebrate gaits, including the amble, the walk, all three pairwise gaits (trot, pace, and gallop), and the pronk are simulated using this property. Rapid gait transitions are simulated in the order--walk, trot, pace, and gallop--that occurs in the cat, along with the observed increase in oscillation frequency. Precise control of quadruped gait switching uses GO-dependent modulation of inhibitory interactions, which generates a different functional anatomy at different arousal levels. The primary human gaits (the walk and the run) and elephant gaits (the amble and the walk) are simulated, without modulation, by oscillations with the same phase relationships but different waveform shapes at different GO signal levels, much as the duty cycles of the feet are longer in the walk than in the run. Relevant neural data from spinal cord, globus pallidus, and motor cortex, among other structures, are discussed.