Research on control strategy of pneumatic soft bionic robot based on improved CPG.

To achieve the accuracy and anti-interference of the motion control of the soft robot more effectively, the motion control strategy of the pneumatic soft bionic robot based on the improved Central Pattern Generator (CPG) is proposed. According to the structure and motion characteristics of the robot, a two-layer neural network topology model for the robot is constructed by coupling 22 Hopfield neuron nonlinear oscillators. Then, based on the Adaptive Neuro-Fuzzy Inference System (ANFIS), the membership functions are offline learned and trained to construct the CPG-ANFIS-PID motion control strategy for the robot. Through simulation research on the impact of CPG-ANFIS-PID input parameters on the swimming performance of the robot, it is verified that the control strategy can quickly respond to input parameter changes between different swimming modes, and stably output smooth and continuous dynamic position signals, which has certain advantages. Then, the motion performance of the robot prototype is analyzed experimentally and compared with the simulation results. The results show that the CPG-ANFIS-PID motion control strategy can output coupled waveform signals stably, and control the executing mechanisms of the pneumatic soft bionic robot to achieve biological rhythms motion propulsion waveforms, confirming that the control strategy has accuracy and anti-interference characteristics, and enable the robot have certain maneuverability, flexibility, and environmental adaptability. The significance of this work lies in establishing a CPG-ANFIS-PID control strategy applicable to pneumatic soft bionic robot and proposing a rhythmic motion control method applicable to pneumatic soft bionic robot.

Beadex, the Drosophila LIM only protein, is required for the growth of the larval neuromuscular junction.

The appropriate growth of the neurons, accurate organization of their synapses, and successful neurotransmission are indispensable for sensorimotor activities. These processes are highly dynamic and tightly regulated. Extensive genetic, molecular, physiological, and behavioral studies have identified many molecular candidates and investigated their roles in various neuromuscular processes. In this article, we show that Beadex (Bx), the Drosophila LIM only (LMO) protein, is required for motor activities and neuromuscular growth of Drosophila. The larvae bearing Bx7, a null allele of Bx, and the RNAi-mediated neuronal-specific knockdown of Bx show drastically reduced crawling behavior, a diminished synaptic span of the neuromuscular junctions (NMJs) and an increased spontaneous neuronal firing with altered motor patterns in the central pattern generators (CPGs). Microarray studies identified multiple targets of Beadex that are involved in different cellular and molecular pathways, including those associated with the cytoskeleton and mitochondria that could be responsible for the observed neuromuscular defects. With genetic interaction studies, we further show that Highwire (Hiw), a negative regulator of synaptic growth at the NMJs, negatively regulates Bx, as the latter's deficiency was able to rescue the phenotype of the Hiw null mutant, HiwDN. Thus, our data indicate that Beadex functions downstream of Hiw to regulate the larval synaptic growth and physiology.NEW & NOTEWORTHY A novel role for Beadex (Bx) regulates the larval neuromuscular junction (NMJ) structure and function in a tissue-specific manner. Bx is expressed in a subset of Toll-6-expressing neurons and is involved in regulating synaptic span and physiology, possibly through its negative interaction with Highwire (Hiw). The findings of this study provide insights into the molecular mechanisms underlying NMJ development and function and warrant further investigation to understand the role of Bx in these processes fully.

Surprising multifunctionality of a Tritonia swim CPG neuron: C2 drives the early phase of postswim crawling despite being silent during the behavior.

In response to a suitably aversive skin stimulus, the marine mollusk Tritonia diomedea launches an escape swim followed by several minutes of high-speed crawling. The two escape behaviors are highly dissimilar: whereas the swim is a muscular behavior involving alternating ventral and dorsal whole body flexions, the crawl is a nonrhythmic gliding behavior mediated by the beating of foot cilia. The serotonergic dorsal swim interneurons (DSIs) are members of the swim central pattern generator (CPG) and also strongly drive crawling. Although the swim network is very well understood, the Tritonia crawling network to date comprises only three neurons: the DSIs and pedal neurons 5 and 21 (Pd5 and Pd21). Since Tritonia's swim network has been suggested to have arisen from a preexisting crawling network, we examined the possible role that another swim CPG neuron, C2, may play in crawling. Because of its complete silence in the postswim crawling period, C2 had not previously been considered to play a role in driving crawling. However, semi-intact preparation experiments demonstrated that a brief C2 spike train surprisingly and strongly drives the foot cilia for ∼30 s, something that cannot be explained by its synaptic connections to Pd5 and Pd21. Voltage-sensitive dye (VSD) imaging in the pedal ganglion identified many candidate crawling motor neurons that fire at an elevated rate after the swim and also revealed several pedal neurons that are strongly excited by C2. It is intriguing that unlike the DSIs, which fire tonically after the swim to drive crawling, C2 does so despite its postswim silence.NEW & NOTEWORTHY Tritonia swim central pattern generator (CPG) neuron C2 surprisingly and strongly drives the early phase of postswim crawling despite being silent during this period. In decades of research, C2 had not been suspected of driving crawling because of its complete silence after the swim. Voltage-sensitive dye imaging revealed that the Tritonia crawling motor network may be much larger than previously known and also revealed that many candidate crawling neurons are excited by C2.

Coupling Relationships between the Brain and the Central Pattern Generator Based on a Fractional-Order Extended Hindmarsh-Rose Model.

BACKGROUND: The states of the central nervous system (CNS) can be classified into subcritical, critical, and supercritical states that endow the system with information capacity, transmission capabilities, and dynamic range. A further investigation of the relationship between the CNS and the central pattern generators (CPG) is warranted to provide insight into the mechanisms that govern the locomotion system. METHODS: In this study, we established a fractional-order CPG model based on an extended Hindmarsh-Rose model with time delay. A CNS model was further established using a recurrent excitation-inhibition neuronal network. Coupling between these CNS and CPG models was then explored, demonstrating a potential means by which oscillations generated by a neural network respond to periodic stimuli. RESULTS AND CONCLUSIONS: These simulations yielded two key sets of findings. First, frequency sliding was observed when the CPG was sent to the CNS in the subcritical, critical, and supercritical states with different external stimulus and fractional-order index values, indicating that frequency sliding regulates brain function on multiple spatiotemporal scales when the CPG and CNS are coupled together. The main frequency range for these simulations was observed in the gamma band. Second, with increasing external inputs the coherence index for the CNS decreases, demonstrating that strong external inputs introduce neuronal stochasticity. Neural network synchronization is then reduced, triggering irregular neuronal firing. Together these results provide novel insight into the potential mechanisms that may underlie the locomotion system.

Swallowing-like activity elicited in neonatal rat medullary slice preparation.

Swallowing is induced by a central pattern generator in the nucleus tractus solitarius (NTS). We aimed to create a medullary slice preparation to elucidate the neural architecture of the central pattern generator of swallowing (Sw-CPG) and record its neural activities. Experiments were conducted on 2-day-old Sprague-Dawley rats (n = 46). The brainstem-spinal cord was transected at the pontomedullary and cervicothoracic junctions; the medulla was sliced transversely at thicknesses of 600, 700, or 800 µm. The rostral end of the slice was 100 µm rostral to the vagus nerve. We recorded hypoglossal nerve activity and electrically stimulated the vagus nerve or microinjected bicuculline methiodide (BIC) into the NTS. The 800-µm slices generated both rhythmic respiratory activity and electrically elicited neural activity. The 700-µm slices generated only respiratory activity, while the 600-µm slices did not generate any neural activity. BIC microinjection into the NTS in 800-µm slices resulted in the typical activity that closely resembled the swallowing activity reported in other experiments. This swallowing-like activity consistently lengthened the respiratory interval. Despite complete inhibition of respiratory activity, weak swallowing-like activity was observed under bath application of a non-NMDA receptor antagonist. Contrastingly, bath application of NMDA receptor antagonists resulted in a complete loss of swallowing-like activity and no change in respiratory activity. These results suggest that the 800-µm medullary slice preparation contains both afferent and efferent neural circuits and pattern generators of swallowing activity. Additionally, NMDA receptors may be necessary for generating swallowing activity. This medullary slice preparation can therefore elucidate Sw-CPG neural networks.

Sparse Firing in a Hybrid Central Pattern Generator for Spinal Motor Circuits.

Central pattern generators are circuits generating rhythmic movements, such as walking. The majority of existing computational models of these circuits produce antagonistic output where all neurons within a population spike with a broad burst at about the same neuronal phase with respect to network output. However, experimental recordings reveal that many neurons within these circuits fire sparsely, sometimes as rarely as once within a cycle. Here we address the sparse neuronal firing and develop a model to replicate the behavior of individual neurons within rhythm-generating populations to increase biological plausibility and facilitate new insights into the underlying mechanisms of rhythm generation. The developed network architecture is able to produce sparse firing of individual neurons, creating a novel implementation for exploring the contribution of network architecture on rhythmic output. Furthermore, the introduction of sparse firing of individual neurons within the rhythm-generating circuits is one of the factors that allows for a broad neuronal phase representation of firing at the population level. This moves the model toward recent experimental findings of evenly distributed neuronal firing across phases among individual spinal neurons. The network is tested by methodically iterating select parameters to gain an understanding of how connectivity and the interplay of excitation and inhibition influence the output. This knowledge can be applied in future studies to implement a biologically plausible rhythm-generating circuit for testing biological hypotheses.

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.

The amyloid precursor protein intracellular domain induces sleep disruptions and its nuclear localization fluctuates in circadian pacemaker neurons in Drosophila and mice.

The most prominent symptom of Alzheimer's disease (AD) is cognitive decline; however, sleep and other circadian disruptions are also common in AD patients. Sleep disruptions have been connected with memory problems and therefore the changes in sleep patterns observed in AD patients may also actively contribute to cognitive decline. However, the underlying molecular mechanisms that connect sleep disruptions and AD are unclear. A characteristic feature of AD is the formation of plaques consisting of Amyloid-ß (Aß) peptides generated by cleavage of the Amyloid Precursor Protein (APP). Besides Aß, APP cleavage generates several other fragments, including the APP intracellular domain (AICD) that has been linked to transcriptional regulation and neuronal homeostasis. Here we show that overexpression of the AICD reduces the early evening expression of two core clock genes and disrupts the sleep pattern in flies. Analyzing the subcellular localization of the AICD in pacemaker neurons, we found that the AICD levels in the nucleus are low during daytime but increase at night. While this pattern of nuclear AICD persisted with age, the nighttime levels were higher in aged flies. Increasing the cleavage of the fly APP protein also disrupted AICD nuclear localization. Lastly, we show that the day/nighttime nuclear pattern of the AICD is also detectable in neurons in the suprachiasmatic nucleus of mice and that it also changes with age. Together, these data suggest that AD-associated changes in APP processing and the subsequent changes in AICD levels may cause sleep disruptions in AD.

Optimization strategies to obtain smooth gait transitions through biologically plausible central pattern generators.

Central pattern generators are small networks that contribute to generating animal locomotion. The models used to study gait generation and gait transition mechanisms often require biologically accurate neuron and synapse models, with high dimensionality and complex dynamics. Tuning the parameters of these models to elicit network dynamics compatible with gait features is not a trivial task, due to the impossibility of inferring a priori the effects of each parameter on the nonlinear system's emergent dynamics. In this paper we explore the use of global optimization strategies for parameter optimization in multigait central pattern generator (CPG) models with complex cell dynamics and minimal topology. We first consider an existing quadruped CPG model as a test bed for the objective function formulation, then proceed to optimize the parameters of a newly proposed multigait, interlimb hexapod CPG model. We successfully obtain hexapod gaits and prompt gait transitions by varying only control currents, while all CPG parameters, once optimized, are kept fixed. This mechanism of gait transitions is compatible with short-term synaptic plasticity.

Circadian Rhythm Regulation by Pacemaker Neuron Chloride Oscillation in Flies.

Circadian rhythms in physiology and behavior sync organisms to external environmental cycles. Here, circadian oscillation in intracellular chloride in central pacemaker neurons of the fly, Drosophila melanogaster, is reviewed. Intracellular chloride links SLC12 cation-coupled chloride transporter function with kinase signaling and the regulation of inwardly rectifying potassium channels.

Roles for cerebellum and subsumption architecture in central pattern generation.

Within vertebrates, central pattern generators drive rhythmical behaviours, such as locomotion and ventilation. Their pattern generation is also influenced by sensory input and various forms of neuromodulation. These capabilities arose early in vertebrate evolution, preceding the evolution of the cerebellum in jawed vertebrates. This later evolution of the cerebellum is suggestive of subsumption architecture that adds functionality to a pre-existing network. From a central-pattern-generator perspective, what additional functionality might the cerebellum provide? The suggestion is that the adaptive filter capabilities of the cerebellum may be able to use error learning to appropriately repurpose pattern output. Examples may include head and eye stabilization during locomotion, song learning, and context-dependent alternation between learnt motor-control sequences.

Investigating the roles of reflexes and central pattern generators in the control and modulation of human locomotion using a physiologically plausible neuromechanical model.

Objective.Studying the neural components regulating movement in human locomotion is obstructed by the inability to perform invasive experimental recording in the human neural circuits. Neuromechanical simulations can provide insights by modeling the locomotor circuits. Past neuromechanical models proposed control of locomotion either driven by central pattern generators (CPGs) with simple sensory commands or by a purely reflex-based network regulated by state-machine mechanisms, which activate and deactivate reflexes depending on the detected gait cycle phases. However, the physiological interpretation of these state machines remains unclear. Here, we present a physiologically plausible model to investigate spinal control and modulation of human locomotion.Approach.We propose a bio-inspired controller composed of two coupled CPGs that produce the rhythm and pattern, and a reflex-based network simulating low-level reflex pathways and Renshaw cells. This reflex network is based on leaky-integration neurons, and the whole system does not rely on changing reflex gains according to the gait cycle state. The musculoskeletal model is composed of a skeletal structure and nine muscles per leg generating movement in sagittal plane.Main results.Optimizing the open parameters for effort minimization and stability, human kinematics and muscle activation naturally emerged. Furthermore, when CPGs were not activated, periodic motion could not be achieved through optimization, suggesting the necessity of this component to generate rhythmic behavior without a state machine mechanism regulating reflex activation. The controller could reproduce ranges of speeds from 0.3 to 1.9 m s-1. The results showed that the net influence of feedback on motoneurons (MNs) during perturbed locomotion is predominantly inhibitory and that the CPGs provide the timing of MNs' activation by exciting or inhibiting muscles in specific gait phases.Significance.The proposed bio-inspired controller could contribute to our understanding of locomotor circuits of the intact spinal cord and could be used to study neuromotor disorders.

Locomotor pattern generation and descending control: a historical perspective.

The ability to generate and control locomotor movements depends on complex interactions between many areas of the nervous system, the musculoskeletal system, and the environment. How the nervous system manages to accomplish this task has been the subject of investigation for more than a century. In vertebrates, locomotion is generated by neural networks located in the spinal cord referred to as central pattern generators. Descending inputs from the brain stem initiate, maintain, and stop locomotion as well as control speed and direction. Sensory inputs adapt locomotor programs to the environmental conditions. This review presents a comparative and historical overview of some of the neural mechanisms underlying the control of locomotion in vertebrates. We have put an emphasis on spinal mechanisms and descending control.

In vivo characterization of the maturation steps of a pigment dispersing factor neuropeptide precursor in the Drosophila circadian pacemaker neurons.

Pigment dispersing factor (PDF) is a key signaling molecule coordinating the neuronal network associated with the circadian rhythms in Drosophila. The precursor (proPDF) of the mature PDF (mPDF) consists of 2 motifs, a larger PDF-associated peptide (PAP) and PDF. Through cleavage and amidation, the proPDF is predicted to produce cleaved-PAP (cPAP) and mPDF. To delve into the in vivo mechanisms underlying proPDF maturation, we generated various mutations that eliminate putative processing sites and then analyzed the effect of each mutation on the production of cPAP and mPDF by 4 different antibodies in both ectopic and endogenous conditions. We also assessed the knockdown effects of processing enzymes on the proPDF maturation. At the functional level, circadian phenotypes were measured for all mutants and knockdown lines. As results, we confirm the roles of key enzymes and their target residues: Amontillado (Amon) for the cleavage at the consensus dibasic KR site, Silver (Svr) for the removal of C-terminal basic residues from the intermediates, PAP-KR and PDF-GK, derived from proPDF, and PHM (peptidylglycine-α-hydroxylating monooxygenase) for the amidation of PDF. Our results suggest that the C-terminal amidation occurs independently of proPDF cleavage. Moreover, the PAP domain is important for the proPDF trafficking into the secretory vesicles and a close association between cPAP and mPDF following cleavage seems required for their stability within the vesicles. These studies highlight the biological significance of individual processing steps and the roles of the PAP for the stability and function of mPDF which is essential for the circadian clockworks.

Rare phenomena of central rhythm and pattern generation in a case of complete spinal cord injury.

Lumbar central pattern generators (CPGs) control the basic rhythm and coordinate muscle activation underlying hindlimb locomotion in quadrupedal mammals. The existence and function of CPGs in humans have remained controversial. Here, we investigated a case of a male individual with complete thoracic spinal cord injury who presented with a rare form of self-sustained rhythmic spinal myoclonus in the legs and rhythmic activities induced by epidural electrical stimulation (EES). Analysis of muscle activation patterns suggested that the myoclonus tapped into spinal circuits that generate muscle spasms, rather than reflecting locomotor CPG activity as previously thought. The EES-induced patterns were fundamentally different in that they included flexor-extensor and left-right alternations, hallmarks of locomotor CPGs, and showed spontaneous errors in rhythmicity. These motor deletions, with preserved cycle frequency and period when rhythmic activity resumed, were previously reported only in animal studies and suggest a separation between rhythm generation and pattern formation. Spinal myoclonus and the EES-induced activity demonstrate that the human lumbar spinal cord contains distinct mechanisms for generating rhythmic multi-muscle patterns.

Central pattern generators evolved for real-time adaptation to rhythmic stimuli.

For a robot to be both autonomous and collaborative requires the ability to adapt its movement to a variety of external stimuli, whether these come from humans or other robots. Typically, legged robots have oscillation periods explicitly defined as a control parameter, limiting the adaptability of walking gaits. Here we demonstrate a virtual quadruped robot employing a bio-inspired central pattern generator (CPG) that can spontaneously synchronize its movement to a range of rhythmic stimuli. Multi-objective evolutionary algorithms were used to optimize the variation of movement speed and direction as a function of the brain stem drive and the centre of mass control respectively. This was followed by optimization of an additional layer of neurons that filters fluctuating inputs. As a result, a range of CPGs were able to adjust their gait pattern and/or frequency to match the input period. We show how this can be used to facilitate coordinated movement despite differences in morphology, as well as to learn new movement patterns.

Two conserved vocal central pattern generators broadly tuned for fast and slow rates generate species-specific vocalizations in Xenopus clawed frogs.

Across phyla, males often produce species-specific vocalizations to attract females. Although understanding the neural mechanisms underlying behavior has been challenging in vertebrates, we previously identified two anatomically distinct central pattern generators (CPGs) that drive the fast and slow clicks of male Xenopus laevis, using an ex vivo preparation that produces fictive vocalizations. Here, we extended this approach to four additional species, X. amieti, X. cliivi, X. petersii, and X. tropicalis, by developing ex vivo brain preparation from which fictive vocalizations are elicited in response to a chemical or electrical stimulus. We found that even though the courtship calls are species-specific, the CPGs used to generate clicks are conserved across species. The fast CPGs, which critically rely on reciprocal connections between the parabrachial nucleus and the nucleus ambiguus, are conserved among fast-click species, and slow CPGs are shared among slow-click species. In addition, our results suggest that testosterone plays a role in organizing fast CPGs in fast-click species, but not in slow-click species. Moreover, fast CPGs are not inherited by all species but monopolized by fast-click species. The results suggest that species-specific calls of the genus Xenopus have evolved by utilizing conserved slow and/or fast CPGs inherited by each species.

Localization of Rhythm Generating Components of the Mammalian Locomotor Central Pattern Generator.

Locomotor movements in mammals are generated by neural networks, situated in the spinal cord, known as central pattern generators (CPGs). Recently, significant strides have been made in the genetic identification of interneuronal components of the locomotor CPG and their specific function. Despite this progress, a population of interneurons that is required for locomotor rhythmogenesis has yet to be identified, and it has been suggested that subsets of interneurons belonging to several genetically-defined populations may be involved. In this study, rather than hunt for rhythmogenic neurons, we take a different approach and attempt to identify the specific region of the spinal cord in which they are located. Focal application of 5-hydroxytryptamine creatine sulfate complex (5-HT) and N-methyl-D-aspartate (NMDA) to the central canal of the rostral lumbar segments of newborn male and female mouse spinal cords quickly generates a robust pattern of fictive locomotion, while inhibition or ablation of neurons in this region disrupts the locomotor rhythm in both rostral and caudal lumbar segments. When applied to the central canal at caudal lumbar levels a higher volume of 5-HT and NMDA are required to elicit fictive locomotion, while inhibition of neurons surrounding the central canal at caudal levels again interrupts rhythmic activity at local segmental levels with minimal effects rostrally. The results of this study indicate that interneurons in the most medial laminae of the neonatal mouse spinal cord are both necessary and sufficient for the generation of locomotor activity, and suggests that this is the region where the rhythm generating core of the locomotor CPG resides.

Control strategy for intraspinal microstimulation based on central pattern generator.

Intraspinal microstimulation (ISMS) is considered as a special functional electrical stimulation (FES) method. This method can restore the movement of paralyzed limbs in patients with spinal cord injury (SCI) using electrical stimulation of spinal cord. There is a special site for central pattern generator (CPG) in the spinal cord. The ISMS acts on the CPG site, and single electrode stimulation produces alternating motion in the hindlimbs of SCI rats. Based on the long short-term memory network (LSTM), a mapping model was established between the stimulation intensity of specific CPG sites and the angle of the knee joint to reflect the motor characteristics of the rat hindlimb. We proposed an LSTM-iterative learning control (ILC) strategy to form a closed-loop control to accurately control hindlimb movement. The proposed LSTM model fits the actual joint angle curve well, and the LSTM-ILC strategy can accurately regulate the hindlimb movement, allowing rats to perform rehabilitation training based on pre-set knee trajectories.