Called Central Pattern Generators Research Articles

Existence of a Long-Range Caudo-Rostral Sensory Influence in Terrestrial Locomotion.

In multisegmented locomotion, coordination of all appendages is crucial for the generation of a proper motor output. In running for example, leg coordination is mainly based on the central interaction of rhythm generating networks, called central pattern generators (CPGs). In slower forms of locomotion, however, sensory feedback, which originates from sensory organs that detect changes in position, velocity and load of the legs' segments, has been shown to play a more crucial role. How exactly sensory feedback influences the activity of the CPGs to establish functional neuronal connectivity is not yet fully understood. Using the female stick insect Carausius morosus, we show for the first time that a long-range caudo-rostral sensory connection exists and highlight that load as sensory signal is sufficient to entrain rhythmic motoneuron (MN) activity in the most rostral segment. So far, mainly rostro-caudal influencing pathways have been investigated where the strength of activation, expressed by the MN activity in the thoracic ganglia, decreases with the distance from the stepping leg to these ganglia. Here, we activated CPGs, producing rhythmic neuronal activity in the thoracic ganglia by using the muscarinic agonist pilocarpine and enforced the stepping of a single, remaining leg. This enabled us to study sensory influences on the CPGs' oscillatory activity. Using this approach, we show that, in contrast to the distance-dependent activation of the protractor-retractor CPGs in different thoracic ganglia, there is no such dependence for the entrainment of the rhythmic activity of active protractor-retractor CPG networks by individual stepping legs.SIGNIFICANCE STATEMENT We show for the first time that sensory information is transferred not only to the immediate adjacent segmental ganglia but also to those farther away, indicating the existence of a long-range caudo-rostral sensory influence. This influence is dependent on stepping direction but independent of whether the leg is actively or passively moved. We suggest that the sensory information comes from unspecific load signals sensed by cuticle mechanoreceptors (campaniform sensilla) of a leg. Our results provide a neuronal basis for the long-established behavioral rules of insect leg coordination. We thus provide a breakthrough in understanding the neuronal networks underlying multilegged locomotion and open new vistas into the neuronal functional connectivity of multisegmented locomotion systems across the animal kingdom.

Neuromorphic Instantiation of Spiking Half-Centered Oscillator Models for Central Pattern Generation.

In both invertebrate and vertebrate animals, small networks called central pattern generators (CPGs) form the building blocks of the neuronal circuits involved in locomotion. Most CPGs contain a simple half-center oscillator (HCO) motif which consists of two neurons, or populations of neurons, connected by reciprocal inhibition. CPGs and HCOs are well characterized neuronal networks and have been extensively modeled at different levels of abstraction. In the past two decades, hardware implementation of spiking CPG and HCO models in neuromorphic hardware has opened up new applications in mobile robotics, computational neuroscience, and neuroprosthetics. Despite their relative simplicity, the parameter space of GPG and HCO models can become exhaustive when considering various neuron models and network topologies. Motivated by computational work in neuroscience that used a brute-force approach to generate a large database of millions of simulations of the heartbeat HCO of the leech, we have started to build a database of spiking chains of multiple HCOs for different neuron model types and network topologies. Here we present preliminary results using the Izhikevich and Morris-Lecar neuron models for single and pairs of HCOs with different inter-HCO coupling schemes.

The roles of ascending sensory signals and top-down central control in the entrainment of a locomotor CPG.

Previous authors have proposed two basic hypotheses about the factors that form the basis of locomotor rhythms in walking insects: sensory feedback only or sensory feedback together with rhythmic activity of small neural circuits called central pattern generators (CPGs). Here we focus on the latter. Following this concept, to generate functional outputs, locomotor control must feature both rhythm generation by CPGs at the level of individual joints and coordination of their rhythmic activities, so that all muscles are activated in an appropriate pattern. This work provides an in-depth analysis of an aspect of this coordination process based on an existing network model of stick insect locomotion. Specifically, we consider how the control system for a single joint in the stick insect leg may produce rhythmic output when subjected to ascending sensory signals from other joints in the leg. In this work, the core rhythm generating CPG component of the joint under study is represented by a classical half-center oscillator constrained by a basic set of experimental observations. While the dynamical features of this CPG, including phase transitions by escape and release, are well understood, we provide novel insights about how these transition mechanisms yield entrainment to the incoming sensory signal, how entrainment can be lost under variation of signal strength and period or other perturbations, how entrainment can be restored by modulation of tonic top-down drive levels, and how these factors impact the duty cycle of the motor output.

Intra- and intersegmental neural network architectures determining rhythmic motor activity in insect locomotion

Abstract The coordinated movement of the extremities of an animal during locomotion is achieved by the interaction between groups of neurons called central pattern generators (CPGs). In the absence of any sensory input this network creates a stable rhythmic motor activity that is essential for a successful coordination between limbs. Studying the structure and the interaction between different parts of the CPG network is therefore of particular interest. This work is motivated by recent experimental results reported by Mantziaris et al. (2017) [12] . By chemically activating both isolated and interconnected deafferented thoracic segments (ganglia) of the stick insect Mantziaris et al. (2017) [12] analyzed the interactions between contralateral networks that drive the levator-depressor muscle pairs, which are responsible for the upward-downward movement of the legs. The results of the experimental analysis showed that intrasegmental phase relations differ between isolated segments. In particular, in isolated segments where the control networks of the middle and hind legs reside, i.e. in the meso- and metathoracic ganglia, the phase relations between activities of the contralateral depressor motoneurons were in-phase and anti-phase, respectively. Moreover, the phase relations switched to in-phase and stabilized when the ganglia were interconnected. Using the phase reduction of an intersegmental network model of stick insect locomotion presented in our previous work (Yeldesbay et al. (2017) [22]), we built a reduced model of the intra- and intersegmental network controlling levator-depressor activity in the meso- and metathoracic ganglia. By examining the intra- and intersegmental phase differences in the model we identified the properties of the network couplings that replicate the results observed in the experiments. We applied the theoretical analysis to escape type CPGs and revealed a set of possible contra- and ipsilateral synaptic connections. Finally, we defined general features of the couplings between CPGs of any type that maintain the phase relations observed in the experiments.

Neuromodulation of central pattern generators and its role in the functional recovery of central pattern generator activity.

Neuromodulators play an important role in how the nervous system organizes activity that results in behavior. Disruption of the normal patterns of neuromodulatory release or production is known to be related to the onset of severe pathologies such as Parkinson's disease, Rett syndrome, Alzheimer's disease, and affective disorders. Some of these pathologies involve neuronal structures that are called central pattern generators (CPGs), which are involved in the production of rhythmic activities throughout the nervous system. Here I discuss the interplay between CPGs and neuromodulatory activity, with particular emphasis on the potential role of neuromodulators in the recovery of disrupted neuronal activity. I refer to invertebrate and vertebrate model systems and some of the lessons we have learned from research on these systems and propose a few avenues for future research. I make one suggestion that may guide future research in the field: neuromodulators restrict the parameter landscape in which CPG components operate, and the removal of neuromodulators may enable a perturbed CPG in finding a new set of parameter values that can allow it to regain normal function.

Design of Synthetic Central Pattern Generators Producing Desired Quadruped Gaits

This paper is concerned with a method for design and analysis of specific neuronal networks, called central pattern generators (CPGs), which produce primary rhythmic patterns in animals. In particular, the paper is focused on synthetic CPGs made up of few basic elements and governing quadrupeds’ gaits and gait transitions, under the control of an external drive. The method combines the principles of bifurcation theory, geometric properties of symmetry, and numerical analysis based on the recently proposed toolbox CEPAGE. The method is applied to two CPGs, one bio-inspired and one purely synthetic. In both the cases, the method provides a way to obtain a desired sequence of gaits by continuously changing a bifurcation parameter related to the external drive.

Neuromodulation of Spinal Locomotor Networks in Rodents.

The basic motor patterns driving rhythmic limb movements during walking are generated by networks of neurons called central pattern generators (CPGs). Within motor control systems, neuromodulators are necessary for proper and efficient CPG function because they induce or regulate essential components of spinal network activity, including firing parameters of CPG neurons and network synaptic strength, allowing the network to change/adapt and sometimes to even become functional. The goal of this work is to focus on classical and recent findings addressing the role of neuromodulators such as glutamate, dopamine, acetylcholine and adenosine in eliciting, changing and sometimes terminating spinal CPG network function in rodents. Neuromodulatory inputs onto CPG locomotor networks have been additionally related to inducing state changes such as locomotor timing, phasing and speed, and to the induction/maintenance of actual network function. These inputs originate from supraspinal centers such as the brainstem and from intraspinal neurotransmission. The isolated in vitro rodent spinal cord preparation is a powerful model for studies on locomotor network organization because of its physiological and anatomical accessibility, as well as the incorporation of various transgenic approaches to identify specific neuronal populations. Both roles are accomplished through the action of neuromodulators on ionotropic and metabotropic receptors mediating synaptic neurotransmission, which can be used by neurons that are intrinsic or extrinsic components of a CPG network itself. This article has hopefully provided a comprehensive overview of some of the main spinal mechanisms involved in the modulatory control of locomotor activity.

Bimodal Respiratory-Locomotor Neurons in the Neonatal Rat Spinal Cord.

Neural networks that can generate rhythmic motor output in the absence of sensory feedback, commonly called central pattern generators (CPGs), are involved in many vital functions such as locomotion or respiration. In certain circumstances, these neural networks must interact to produce coordinated motor behavior adapted to environmental constraints and to satisfy the basic needs of an organism. In this context, we recently reported the existence of an ascending excitatory influence from lumbar locomotor CPG circuitry to the medullary respiratory networks that is able to depolarize neurons of the parafacial respiratory group during fictive locomotion and to subsequently induce an increased respiratory rhythmicity (Le Gal et al., 2014b). Here, using an isolated in vitro brainstem-spinal cord preparation from neonatal rat in which the respiratory and the locomotor networks remain intact, we show that during fictive locomotion induced either pharmacologically or by sacrocaudal afferent stimulation, the activity of both thoracolumbar expiratory motoneurons and interneurons is rhythmically modulated with the locomotor activity. Completely absent in spinal inspiratory cells, this rhythmic pattern is highly correlated with the hindlimb ipsilateral flexor activities. Furthermore, silencing brainstem neural circuits by pharmacological manipulation revealed that this locomotor-related drive to expiratory motoneurons is solely dependent on propriospinal pathways. Together these data provide the first evidence in the newborn rat spinal cord for the existence of bimodal respiratory-locomotor motoneurons and interneurons onto which both central efferent expiratory and locomotor drives converge, presumably facilitating the coordination between the rhythmogenic networks responsible for two different motor functions. Significance statement: In freely moving animals, distant regions of the brain and spinal cord controlling distinct motor acts must interact to produce the best adapted behavioral response to environmental constraints. In this context, it is well established that locomotion and respiration must to be tightly coordinated to reduce muscular interferences and facilitate breathing rate acceleration during exercise. Here, using electrophysiological recordings in an isolated in vitro brainstem-spinal cord preparation from neonatal rat, we report that the locomotor-related signal produced by the lumbar central pattern generator for locomotion selectively modulates the intracellular activity of spinal respiratory neurons engaged in expiration. Our results thus contribute to our understanding of the cellular bases for coordinating the rhythmic neural circuitry responsible for different behaviors.

2A2-S04 足底感覚情報を活用した二足歩行制御則の実験的検証

It is well-known that a neural circuit in a spinal cord called central pattern generator (CPG) plays a crucial role to generate stable and adaptive bipedal walking. Although various CPG models have been proposed so far, the essential mechanism has not been clarified: neural connections in CPG and sensory feedback have been designed on ad-hoc basis. To reconsider the design principle of CPG model for bipedal walking, we extended our quadruped CPG, which fully exploits physical interaction yielded from local load sensing, to bipedal walking control, based on the phylogeny process. In this study, we developed a bipedal robot that has load sensors in the plantar area for experimental verification of our bipedal walking model.

2A2-S01 環境からの手応えを活用する四脚ロボットのCPG制御

Quadrupeds exhibit adaptive locomotion under real-world environment. Such locomotion is generated via the coordination between legs, i. e., interlimb coordination and is controlled by a neural network called central pattern generator (CPG). However, underlying mechanism remains elusive. To establish the design principle of highly adaptive quadruped locomotion, we propose a "TEGOTAE"-based CPG control that exploits vertical and horizontal ground reaction forces (GRFs) from environment. In this paper, we develop a quadruped robot with GRF sensing mechanism and verify the validity of proposed control scheme.

Removing sensory input disrupts spinal locomotor activity in the early postnatal period

Motor patterns driving rhythmic movements of our lower limbs during walking are generated by groups of neurons within the spinal cord, called central pattern generators (CPGs). After suffering a spinal cord injury (SCI), many descending fibers from our brain are severed or become nonfunctional, leaving the spinal CPG network without its initiating drive. Recent studies have focused on the importance of maintaining sensory stimulation to the limbs of SCI patients as a way to initiate and control the CPG locomotor network. We began assessing the role of sensory feedback to the locomotor CPG network using a neonatal mouse spinal cord preparation where the hindlimbs are still attached. Removing sensory feedback coming from the hindlimbs by way of a lower lumbar transection or by ventral root denervation revealed a positive correlation in the ability of sensory input deprivation to disrupt ongoing locomotor activity on older versus younger animals. The differences in the motor responses as a function of age could be correlated with the loss of excitatory activity from sensory afferents. Continued studies on this field could eventually provide key information that translates into the design of novel therapeutic strategies to treat patients who have suffered a SCI.

Activity-dependent Synaptic Plasticity and Metaplasticity in Spinal Motor Networks

Throughout life, neuronal network properties are modulated according to both external and internal stimuli. These adaptive capabilities of the central nervous system (CNS) have been generically termed "plasticity". One prominent form of CNS plasticity is the capability of synapses to change their strength. Synaptic strength is not a constant value but depends at each moment on the synapse's past activity. These changes in transmission efficacy are called activity-dependent synaptic plasticity (ADSP) and result in an increase (potentiation) or a decrease (depression) in synaptic strength. The ability of synapses to express one type of ADSP can change as a function of previous plasticity and previous activation of synapses. This plasticity of synaptic plasticity has been termed metaplasticity. ADSP and metaplasticity are now regarded as essential mechanisms for normal information processing in neuronal networks. Rhythmic activities such as locomotion are generated by rhythmically active central neuronal networks called central pattern generators (CPGs) that possess the intrinsic ability to generate rhythmic and organized activity in the absence of sensory inputs. The CPG activity arises from a complex dynamic interaction between synaptic transmission, intrinsic membrane properties and neuromodulatory inputs. A growing body of evidence suggests that the spinal cord matches the plastic and metaplastic properties found in other parts of the CNS, both under normal conditions and after spinal cord injury. Here, findings describing ADSP and its neuromodulation in vertebrate sensorimotor networks are reviewed, followed by a discussion of the potential role of ADSP and neuromodulation in the physiology and pathophysiology of motor circuit assembly.

Irregular Breathing in Mice following Genetic Ablation of V2a Neurons

Neural networks called central pattern generators (CPGs) generate repetitive motor behaviors such as locomotion and breathing. Glutamatergic neurons are required for the generation and inhibitory neurons for the patterning of the motor activity associated with repetitive motor behaviors. In the mouse, glutamatergic V2a neurons coordinate the activity of left and right leg CPGs in the spinal cord enabling mice to generate an alternating gait. Here, we investigate the role of V2a neurons in the neural control of breathing, an essential repetitive motor behavior. We find that, following the ablation of V2a neurons, newborn mice breathe at a lower frequency. Recordings of respiratory activity in brainstem-spinal cord and respiratory slice preparations demonstrate that mice lacking V2a neurons are deficient in central respiratory rhythm generation. The absence of V2a neurons in the respiratory slice preparation can be compensated for by bath application of neurochemicals known to accelerate the breathing rhythm. In this slice preparation, V2a neurons exhibit a tonic firing pattern. The existence of direct connections between V2a neurons in the medial reticular formation and neurons of the pre-Bötzinger complex indicates that V2a neurons play a direct role in the function of the respiratory CPG in newborn mice. Thus, neurons of the embryonic V2a lineage appear to have been recruited to neural networks that control breathing and locomotion, two prominent CPG-driven, repetitive motor behaviors.

A bio-inspired approach for online trajectory generation of industrial robots

This paper presents a bio-inspired approach for generating online rhythmic point-to-point motions commonly used by industrial robots. Rhythmic motions in biological systems are produced with neural circuits called central pattern generators (CPGs). A modified form of CPG network is designed and used to generate the rhythmic motion. A pick and place task is considered an industrial application of the proposed approach. Several pick and place applications are considered. It is demonstrated that with CPGs, online changes of rhythmic trajectories are successfully generated. The proposed approach is novel, enables online trajectory generation, improves machine life and yields excellent coordinated natural motion for the robotic systems.

Role of STDP in regulation of neural timing networks in human: a simulation study

Many physiological events require an accurate timing signal, usually generated by neural networks called central pattern generators (CPGs). On the other hand, properties of neurons and neural networks (e.g. time constants of neurons and weights of network connections) alter with time, resulting in gradual changes in timing of such networks. Recently, a synaptic weight adjustment mechanism has been docu¬mented in some synapses, based on timing of pre- and post-synaptic electrical activities, called s spike-timing-dependent plasticity (STDP). We present a model in which the accuracy of the timer network sig¬nificantly improves by using this mechanism. In our model, based on leaky integrate and fire elements, we used 30 timer neurons (time constant=0.0005, resting voltage=-60 mv and threshold=-50 mv) and one feedback neuron (Time constant=0.001, resting voltage=-60 mv, threshold=-50 mv). Some simulated noise was applied to the synaptic connections (random deviation up to 20% of the default synaptic weight). We applied STDP to feedback neuron-timer neurons connections (for both long term depression and long term potentiation: dw=0.01×e-(ISI/100+1) and examined the inter-spike interval (ISI) of the feedback neuron as our model output. There was a significant reduction in ISI variation with (Mean ISI=230 and SD=2.21) and without (Mean ISI=204, SD=10.1) applying STDP. In this simulation, weak synapses will be strengthened because their post-synaptic timer neuron will fire after feedback neuron (long term potentiation) and strong synapses will be weakened because their post-synaptic timer neuron will fire before feedback neuron (long term depression). Therefore, the effect of noise would be partially compensated.

The role of inhibitory neurotransmission in locomotor circuits of the developing mammalian spinal cord

Neuronal circuits generating the basic coordinated limb movements during walking of terrestrial mammals are localized in the spinal cord. In these neuronal circuits, called central pattern generators (CPGs), inhibitory synaptic transmission plays a crucial part. Inhibitory synaptic transmission mediated by glycine and GABA is thought to be essential in coordinated activation of muscles during locomotion, in particular, controlling temporal and spatial activation patterns of muscles of each joint of each limb on the left and right side of the body. Inhibition is involved in other aspects of locomotion such as control of speed and stability of the rhythm. However, the precise roles of neurotransmitters and their receptors mediating inhibitory synaptic transmission in mammalian spinal CPGs remain unclear. Moreover, many of the inhibitory interneurones essential for output pattern of the CPG are yet to be identified. In this review, recent advances on these issues, mainly from studies in the developing rodent spinal cord utilizing electrophysiology, molecular and genetic approaches are discussed.

Optogenetic dissection of a behavioural module in the vertebrate spinal cord

Locomotion relies on neural networks called central pattern generators (CPGs) that generate periodic motor commands for rhythmic movements1. We have identified a spinal input to the CPG that drives spontaneous locomotion using a combination of intersectional gene expression and optogenetics2 in zebrafish larvae. The photo-stimulation of one specific cell type was sufficient to induce a symmetrical tail beating sequence that mimics spontaneous slow forward swimming. This neuron is the Kolmer-Agduhr (KA) cell3, which extends cilia into the central cerebrospinal fluid containing canal of the spinal cord and has an ipsilateral ascending axon that terminates in a series of consecutive segments4. Genetically silencing KA cells reduced the frequency of spontaneous free swimming, indicating that KA cell activity provides necessary tone for spontaneous forward swimming. KA cells have been known for over 75 years, but their function has been mysterious. Our results reveal that during early development in low vertebrates these cells provide a positive drive to the spinal CPG for spontaneous locomotion.

Gait planning for quadruped robot based on dynamic stability: landing accordance ratio

In this article, the method for increasing dynamic stability of quadruped robot is proposed. Previous researches on dynamic walking of quadruped robots have used only walking pattern called central pattern generator (CPG). In this research, different from walking generation with only CPG, a instinctive stability measure called landing accordance ratio, is proposed and used for increasing dynamic stability. In addition, dynamic balance control and control to adjust walking trajectory for increasing dynamic stability measure is also proposed. Proposed methods are verified with dynamic simulation and a large number of experiments with quadruped robot platform.

Altered Gravity Highlights Central Pattern Generator Mechanisms

In many nonprimate species, rhythmic patterns of activity such as locomotion or respiration are generated by neural networks at the spinal level. These neural networks are called central pattern generators (CPGs). Under normal gravitational conditions, the energy efficiency and the robustness of human rhythmic movements are due to the ability of CPGs to drive the system at a pace close to its resonant frequency. This property can be compared with oscillators running at resonant frequency, for which the energy is optimally exchanged with the environment. However, the ability of the CPG to adapt the frequency of rhythmic movements to new gravitational conditions has never been studied. We show here that the frequency of a rhythmic movement of the upper limb is systematically influenced by the different gravitational conditions created in parabolic flight. The period of the arm movement is shortened with increasing gravity levels. In weightlessness, however, the period is more dependent on instructions given to the participants, suggesting a decreased influence of resonant frequency. Our results are in agreement with a computational model of a CPG coupled to a simple pendulum under the control of gravity. We demonstrate that the innate modulation of rhythmic movements by CPGs is highly flexible across gravitational contexts. This further supports the involvement of CPG mechanisms in the achievement of efficient rhythmic arm movements. Our contribution is of major interest for the study of human rhythmic activities, both in a normal Earth environment and during microgravity conditions in space.

The role of postinhibitory rebound in the locomotor central-pattern generator of Clione limacina

In animals, networks of central neurons, called central-pattern generators (CPGs), produce a variety of locomotory behaviors including walking, swimming, and flying. CPGs from diverse animals share many common characteristics that function at the system level, circuit level, and cellular level. However, the relative roles of common CPG characteristics are variable among different animal species, in ways that suit different forms of locomotion in different environmental contexts. Here, we examine some of these common features within the locomotor CPG in a model system used to investigate changes in locomotory speed-the swim system of the pteropod mollusk, Clione limacina. In particular, we discuss the role of one cellular characteristic that is essential for locomotor pattern generation in Clione, postinhibitory rebound.