Central respiratory pattern generation in the bullfrog, Rana catesbeiana

There are two components to breathing pattern generation the production of the pattern of neural discharge associated with individual breaths, and the pattern in which breaths are produced to effect ventilation. Bullfrogs typically breathe with randomly distributed breaths. When respiratory drive is elevated, breathing becomes more regular and often episodic. Studies on in vitro brainstem-spinal cord preparations of the adult bullfrog and in situ preparations of decerebrate, paralyzed, unidirectionally ventilated animals suggest that output from the central rhythm generator in frogs is conditional on receiving some input and that a host of central inputs remain even in the most reduced preparations. There appear to be descending inputs from sites in the dorsal brainstem just caudal to the optic chiasma that cluster breaths into episodes, a strong excitatory input caudal to this site but rostral to the origin of the Vth cranial nerve and, possibly, segmental rhythm generators throughout the medulla that are normally entrained to produce the normal breathing pattern. The data also suggest that the shape of the discharge pattern (augmenting, decrementing) and timing of outputs (alternating vs synchronous) associated with motor outflow during each breath are also dependent on the interconnections between these various sites.     

Effects of maturation and acidosis on the chaos-like complexity of the neural respiratory output in the isolated brainstem of the tadpole, Rana esculenta

Human ventilation at rest exhibits mathematical chaos-like complexity that can be described as long-term unpredictability mediated (in whole or in part) by some low-dimensional nonlinear deterministic process. Although various physiological and pathological situations can affect respiratory complexity, the underlying mechanisms remain incompletely elucidated. If such chaos-like complexity is an intrinsic property of central respiratory generators, it should appear or increase when these structures mature or are stimulated. To test this hypothesis, we employed the isolated tadpole brainstem model [Rana (Pelophylax) esculenta] and recorded the neural respiratory output (buccal and lung rhythms) of pre- (n = 8) and postmetamorphic tadpoles (n = 8), at physiologic (7.8) and acidic pH (7.4). We analyzed the root mean square of the cranial nerve V or VII neurograms. Development and acidosis had no effect on buccal period. Lung frequency increased with development (P < 0.0001). It also increased with acidosis, but in postmetamorphic tadpoles only (P < 0.05). The noise-titration technique evidenced low-dimensional nonlinearities in all the postmetamorphic brainstems, at both pH. Chaos-like complexity, assessed through the noise limit, increased from pH 7.8 to pH 7.4 (P < 0.01). In contrast, linear models best fitted the ventilatory rhythm in all but one of the premetamorphic preparations at pH 7.8 (P < 0.005 vs. postmetamorphic) and in four at pH 7.4 (not significant vs. postmetamorphic). Therefore, in a lower vertebrate model, the brainstem respiratory central rhythm generator accounts for ventilatory chaos-like complexity, especially in the postmetamorphic stage and at low pH. According to the ventilatory generators homology theory, this may also be the case in mammals.     

Evaluating functional roles of phase resetting in generation of adaptive human bipedal walking with a physiologically based model of the spinal pattern generator

The central pattern generators (CPGs) in the spinal cord strongly contribute to locomotor behavior. To achieve adaptive locomotion, locomotor rhythm generated by the CPGs is suggested to be functionally modulated by phase resetting based on sensory afferent or perturbations. Although phase resetting has been investigated during fictive locomotion in cats, its functional roles in actual locomotion have not been clarified. Recently, simulation studies have been conducted to examine the roles of phase resetting during human bipedal walking, assuming that locomotion is generated based on prescribed kinematics and feedback control. However, such kinematically based modeling cannot be used to fully elucidate the mechanisms of adaptation. In this article we proposed a more physiologically based mathematical model of the neural system for locomotion and investigated the functional roles of phase resetting. We constructed a locomotor CPG model based on a two-layered hierarchical network model of the rhythm generator (RG) and pattern formation (PF) networks. The RG model produces rhythm information using phase oscillators and regulates it by phase resetting based on foot-contact information. The PF model creates feedforward command signals based on rhythm information, which consists of the combination of five rectangular pulses based on previous analyses of muscle synergy. Simulation results showed that our model establishes adaptive walking against perturbing forces and variations in the environment, with phase resetting playing important roles in increasing the robustness of responses, suggesting that this mechanism of regulation may contribute to the generation of adaptive human bipedal locomotion.     

Mathematical model of activity of spinal generators producing rhythmic movement

Different organizational arrangements of scratching and locomotor rhythm generators were simulated by a computer-aided mathematical model. A functional group of neurons (a hemicenter constructed on the basis of a stochastically arranged neuronal network) served as the basis for the generator. Several organizational arrangements of scratching and locomotor rhythm generators are considered: two hemicenters with reciprocal inhibitory connections and tonic excitatory influences on both; two hemicenters with inhibitory-excitatory connections and tonic excitatory influences on only one of these; circular structures consisting of more than two functional groups of neurons with excitatory and inhibitory connections between them. All these arrangements would allow for generation of rhythmic activity with a similar time course to that of scratching and locomotor rhythm. It was found that the transition from locomotor to scratching rhythm could be based on fairly simply organized effects on generator neurons. Principles possibly guiding the construction of spinal generators of scratching and locomotor movements are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 20, No. 5, pp. 586–597, September–October, 1988.     

Caenorhabditis elegans body wall muscles are simple actuators

Over the past four decades, one of the simplest nervous systems across the animal kingdom, that of the nematode worm Caenorhabditis elegans, has drawn increasing attention. This system is the subject of an intensive concerted effort to understand the behaviour of an entire living animal, from the bottom up and the top down. C. elegans locomotion, in particular, has been the subject of a number of models, but there is as yet no general agreement about the key (rhythm generating) elements. In this paper we investigate the role of one component of the locomotion subsystem, namely the body wall muscles, with a focus on the role of inter-muscular gap junctions. We construct a detailed electrophysiological model which suggests that these muscles function, to a first approximation, as mere actuators and have no obvious rhythm generating role. Furthermore, we show that within our model inter-muscular coupling is too weak to have a significant electrical effect. These results rule out muscles as key generators of locomotion, pointing instead to neural activity patterns. More specifically, the results imply that the reduced locomotion velocity observed in unc-9 mutants is likely to be due to reduced neuronal rather than inter-muscular coupling.     

Neuromodulation of central pattern generators in invertebrates and vertebrates

Central pattern generators are subject to extensive modulation that generates flexibility in the rhythmic outputs of these neural networks. The effects of neuromodulators interact with one another, and modulatory neurons are themselves often subject to modulation, enabling both higher order control and indirect interactions among central pattern generators. In addition, modulators often directly mediate the interactions between functionally related central pattern generators. In systems such as the vertebrate respiratory central pattern generator, multiple pacemaker types interact to produce rhythmic output. Modulators can then alter the relative contributions of the different pacemakers, leading to substantial changes in motor output and hence to different behaviors. Surprisingly, substantial changes in some aspects of the circuitry of a central pattern generator, such as a several-fold increase in synaptic strength, can sometimes have little effect on the output of the CPG, whereas other changes have profound effects.     

Intersegmental coordination of swimmeret rhythms in isolated nerve cords of crayfish

Summary In crayfish,Pacifastacus leniusculus, abdominal ganglia that can generate the motor pattern normally associated with swimmeret beating continue to do so when the number of connected ganglia is reduced from six to two. The period and phase of the rhythm produced by these shortened chains of ganglia are the same as those produced by the full abdominal nerve cord. These results demonstrate that interactions between any two neighboring ganglia suffice to establish the metachronal phase-lag characteristic of the swimmeret rhythm.Several kinds of interganglionic interneurons that are part of the swimmeret system originate in each abdominal ganglion. These premotor interneurons receive synaptic input in the ganglion of origin and project to other ganglia. Axons from interganglionic neurons also terminate in each ganglion, and some of these terminals receive PSPs from the swimmeret pattern generators in the ganglion where they terminate. Currents injected into these interneurons and axon terminals can reset the swimmeret rhythm. These results demonstrate that premotor interganglionic interneurons exist that have the properties required to coordinate adjacent ganglia. The structures and physiological properties of these interneurons are described and discussed in the context of Stein's model of intersegmental coordination in the swimmeret system.     

Synaptic patterning of left-right alternation in a computational model of the rodent hindlimb central pattern generator

Establishing, maintaining, and modifying the phase relationships between extensor and flexor muscle groups is essential for central pattern generators in the spinal cord to coordinate the hindlimbs well enough to produce the basic walking rhythm. This paper investigates a simplified computational model for the spinal hindlimb central pattern generator (CPG) that is abstracted from experimental data from the rodent spinal cord. This model produces locomotor-like activity with appropriate phase relationships in which right and left muscle groups alternate while extensor and flexor muscle groups alternate. Convergence to this locomotor pattern is slow, however, and the range of parameter values for which the model produces appropriate output is relatively narrow. We examine these aspects of the model’s coordination of left-right activity through investigation of successively more complicated subnetworks, focusing on the role of the synaptic architecture in shaping motoneuron phasing. We find unexpected sensitivity in the phase response properties of individual neurons in response to stimulation and a need for high levels of both inhibition and excitation to achieve the walking rhythm. In the absence of cross-cord excitation, equal levels of ipsilateral and contralateral inhibition result in a strong preference for hopping over walking. Inhibition alone can produce the walking rhythm, but contralateral inhibition must be much stronger than ipsilateral inhibition. Cross-cord excitatory connections significantly enhance convergence to the walking rhythm, which is achieved most rapidly with strong crossed excitation and greater contralateral than ipsilateral inhibition. We discuss the implications of these results for CPG architectures based on unit burst generators.     

The pineal organ of teleost fishes

The pineal organ of teleost fish is a directly photosensory organ that contains photoreceptor cells similar to those of the retina. It conveys photoperiod information to the brain via neural pathways and by release of indoleamines, primarily melatonin, into the circulation. The photoreceptor cells respond to changes in ambient illumination with a gradual modulation of neurotransmission to second-order neurons that innervate various brain centres, and by modulation of indoleamine synthesis. Melatonin is produced rhythmically, and melatonin synthesis may be regulated either directly by ambient photoperiod, or by an endogenous circadian oscillator that is entrained by the photoperiod. During natural conditions, melatonin is produced at highest levels during the night. Although the pineal organ undoubtedly influences a variety of physiological parameters, as assessed by experimental removal of the pineal organ and/or administration of exogenous indoleamines, its role in any physiological situation is not clear cut. The effects of any interference with pineal functions appear to vary with the time of year and experimental photothermal regimes. There are strong indications that the pineal organ is one component in a central neural system that constitutes the photoperiod-responding system of the animal, i.e. the system that is responsible for correct timing of daily and seasonal physiological rhythms. It is important to envisage the pineal organ as a part of this system; it interacts with other photosensory structures (the retina, possibly extraretinal non-pineal photoreceptors) and circadian rhythm generators     

Simulation of the hippocampal theta rhythm

Centre of Theoretical and Computational Neuroscience, University of Plymouth, UK Basing on the hypothesis about the mechanisms of the theta rhythm generation, the article presents mathematical and computational models of theta activity in the hippocampus. The problem of the theta rhythm modeling is nontrivial because the slow theta oscillations (about 5 Hz) should be generated by a neural system composed of frequently firing neural populations. We studied a model of neural pacemakers in the septum. In this model, the pacemaker follows the frequency of the external signal if this frequency does not deviate too far from the natural frequency of the pacemaker, otherwise the pacemaker returns to the frequency of its own oscillations. These results are in agreement with the experimental records of medial septum neurons. Our model of the septal pacemaker of the theta rhythm is based on the hypothesis that the hippocampal theta appears as a result of the influence of the assemblies of neurons in the medial septum which are under control of pacemaker neurons. Though the model of the pacemaker satisfies many experimental facts, the synchronization of activity in different neural assemblies of the model is not as strong as it should be. Another model of the theta generation is based on the anatomical data about the existence of the inhibitory GABAergic loop between the medial septum and the hippocampus. This model shows stable oscillations at the frequency of the theta rhythm in a broad range of parameter values. It also provides explanation to the experimental data about the variation of the frequency and the amplitude of the theta rhythm under different external stimulations of the system. The role of the theta rhythm for information processing in the hippocampus is discussed.     

Pre-/post-otic rhombomeric interactions control the emergence of a fetal-like respiratory rhythm in the mouse embryo

How regional patterning of the neural tube in vertebrate embryos may influence the emergence and the function of neural networks remains elusive. We have begun to address this issue in the embryonic mouse hindbrain by studying rhythmogenic properties of different neural tube segments. We have isolated pre- and post-otic hindbrain segments and spinal segments of the mouse neural tube, when they form at embryonic day (E) 9, and grafted them into the same positions in stage-matched chick hosts. Three days after grafting, in vitro recordings of the activity in the cranial nerves exiting the grafts indicate that a high frequency (HF) rhythm (order: 10 bursts/min) is generated in post-otic segments while more anterior pre-otic and more posterior spinal territories generate a low frequency (LF) rhythm (order: 1 burst/min). Comparison with homo-specific grafting of corresponding chick segments points to conservation in mouse and chick of the link between the patterning of activities and the axial origin of the hindbrain segment. This HF rhythm is reminiscent of the respiratory rhythm known to appear at E15 in mice. We also report on pre-/post-otic interactions. The pre-otic rhombomere 5 prevents the emergence of the HF rhythm at E12. Although the nature of the interaction with r5 remains obscure, we propose that ontogeny of fetal-like respiratory circuits relies on: (i) a selective developmental program enforcing HF rhythm generation, already set at E9 in post-otic segments, and (ii) trans-segmental interactions with pre-otic territories that may control the time when this rhythm appears.     

Relationship between Neural Rhythm Generation Disorders and Physical Disabilities in Parkinson’s Disease Patients’ Walking

Walking is generated by the interaction between neural rhythmic and physical activities. In fact, Parkinson’s disease (PD), which is an example of disease, causes not only neural rhythm generation disorders but also physical disabilities. However, the relationship between neural rhythm generation disorders and physical disabilities has not been determined. The aim of this study was to identify the mechanism of gait rhythm generation. In former research, neural rhythm generation disorders in PD patients’ walking were characterized by stride intervals, which are more variable and fluctuate randomly. The variability and fluctuation property were quantified using the coefficient of variation (CV) and scaling exponent α. Conversely, because walking is a dynamic process, postural reflex disorder (PRD) is considered the best way to estimate physical disabilities in walking. Therefore, we classified the severity of PRD using CV and α. Specifically, PD patients and healthy elderly were classified into three groups: no-PRD, mild-PRD, and obvious-PRD. We compared the contributions of CV and α to the accuracy of this classification. In this study, 45 PD patients and 17 healthy elderly people walked 200 m. The severity of PRD was determined using the modified Hoehn–Yahr scale (mH-Y). People with mH-Y scores of 2.5 and 3 had mild-PRD and obvious-PRD, respectively. As a result, CV differentiated no-PRD from PRD, indicating the correlation between CV and PRD. Considering that PRD is independent of neural rhythm generation, this result suggests the existence of feedback process from physical activities to neural rhythmic activities. Moreover, α differentiated obvious-PRD from mild-PRD. Considering α reflects the intensity of interaction between factors, this result suggests the change of the interaction. Therefore, the interaction between neural rhythmic and physical activities is thought to plays an important role for gait rhythm generation. These characteristics have potential to evaluate the symptoms of PD.     

Reflexes and preflexes: on the role of sensory feedback on rhythmic patterns in insect locomotion

Neuromuscular systems are stabilized and controlled by both feedforward and feedback signals. Feedforward pathways driven by central pattern generators (CPGs), in conjunction with preflexive mechanical reaction forces and nonlinear muscle properties, can produce stable stereotypical gaits. Feedback is nonetheless present in both slow and rapid running, and preflexive mechanisms can join with neural reflexes originating in proprioceptive sensors to yield robust behavior in uncertain environments. Here, we develop a single degree-of-freedom neuromechanical model representing a joint actuated by an agonist/antagonist muscle pair driven by motoneurons and a CPG in a periodic rhythm characteristic of locomotion. We consider two characteristic feedback modes: phasic and tonic. The former encodes states such as position in the timing of individual spikes, while the latter can transmit graded measures of force and other continuous variables as spike rates. We use results from phase reduction and averaging theory to predict phase relationships between CPG and motoneurons in the presence of feedback and compare them with simulations of the neuromechanical model, showing that both phasic and tonic feedback can shift motoneuronal timing and thereby affect joint motions. We find that phase changes in neural activation can cooperate with preflexive displacement and velocity effects on muscle force to compensate for externally applied forces, and that these effects qualitatively match experimental observations in the cockroach.     

Multi-layered multi-pattern CPG for adaptive locomotion of humanoid robots

In this paper, we present an extended mathematical model of the central pattern generator (CPG) in the spinal cord. The proposed CPG model is used as the underlying low-level controller of a humanoid robot to generate various walking patterns. Such biological mechanisms have been demonstrated to be robust in locomotion of animal. Our model is supported by two neurophysiological studies. The first study identified a neural circuitry consisting of a two-layered CPG, in which pattern formation and rhythm generation are produced at different levels. The second study focused on a specific neural model that can generate different patterns, including oscillation. This neural model was employed in the pattern generation layer of our CPG, which enables it to produce different motion patterns—rhythmic as well as non-rhythmic motions. Due to the pattern-formation layer, the CPG is able to produce behaviors related to the dominating rhythm (extension/flexion) and rhythm deletion without rhythm resetting. The proposed multi-layered multi-pattern CPG model (MLMP-CPG) has been deployed in a 3D humanoid robot (NAO) while it performs locomotion tasks. The effectiveness of our model is demonstrated in simulations and through experimental results.     

A Beamformer Analysis of MEG Data Reveals Frontal Generators of the Musically Elicited Mismatch Negativity

To localize the neural generators of the musically elicited mismatch negativity with high temporal resolution we conducted a beamformer analysis (Synthetic Aperture Magnetometry, SAM) on magnetoencephalography (MEG) data from a previous musical mismatch study. The stimuli consisted of a six-tone melodic sequence comprising broken chords in C- and G-major. The musical sequence was presented within an oddball paradigm in which the last tone was lowered occasionally (20%) by a minor third. The beamforming analysis revealed significant right hemispheric neural activation in the superior temporal (STC), inferior frontal (IFC), superior frontal (SFC) and orbitofrontal (OFC) cortices within a time window of 100–200 ms after the occurrence of a deviant tone. IFC and SFC activation was also observed in the left hemisphere. The pronounced early right inferior frontal activation of the auditory mismatch negativity has not been shown in MEG studies so far. The activation in STC and IFC is consistent with earlier electroencephalography (EEG), optical imaging and functional magnetic resonance imaging (fMRI) studies that reveal the auditory and inferior frontal cortices as main generators of the auditory MMN. The observed right hemispheric IFC is also in line with some previous music studies showing similar activation patterns after harmonic syntactic violations. The results demonstrate that a deviant tone within a musical sequence recruits immediately a distributed neural network in frontal and prefrontal areas suggesting that top-down processes are involved when expectation violation occurs within well-known stimuli.     

Theories of bipedal walking: an odyssey

In this paper six theories of bipedal walking, and the evidence in support of the theories, are reviewed. They include: evolution, minimising energy consumption, maturation in children, central pattern generators, linking control and effect, and robots on two legs. Specifically, the six theories posit that: (1) bipedalism is the fundamental evolutionary adaptation that sets hominids--and therefore humans--apart from other primates; (2) locomotion is the translation of the centre of gravity along a pathway requiring the least expenditure of energy; (3) when a young child takes its first few halting steps, his or her biomechanical strategy is to minimise the risk of falling; (4) a dedicated network of interneurons in the spinal cord generates the rhythm and cyclic pattern of electromyographic signals that give rise to bipedal gait; (5) bipedal locomotion is generated through global entrainment of the neural system on the one hand, and the musculoskeletal system plus environment on the other; and (6) powered dynamic gait in a bipedal robot can be realised only through a strategy which is based on stability and real-time feedback control. The published record suggests that each of the theories has some measure of support. However, it is important to note that there are other important theories of locomotion which have not been covered in this review. Despite such omissions, this odyssey has explored the wide spectrum of bipedal walking, from its origins through to the integration of the nervous, muscular and skeletal systems.     

A Bionic Neural Network for Fish-Robot Locomotion

A bionic neural network for fish-robot locomotion is presented. The bionic neural network inspired from fish neural net- work consists of one high level controller and one chain of central pattern generators （CPGs）. Each CPG contains a nonlinear neural Zhang oscillator which shows properties similar to sine-cosine model. Simulation re, suits show that the bionic neural network presents a good performance in controlling the fish-robot to execute various motions such as startup, stop, forward swimming, backward swimming, turn right and turn left.     

Active selection of afferent information as the basic principle of peripheral correction of the activity of spinal rhythmic movement generators

This paper summarizes information obtained in the experimental study of the dynamics of polarization of central primary afferent endings and modifications of segmental responses to afferent stimuli during fictitious locomotion and fictitious scratching in immobilized, decorticated, decerebrate, and spinal cats. Fictitious locomotion was accompanied by tonic hyperpolarization, fictitious scratching by tonic depolarization of central primary afferent endings. Against the background of these long-lasting changes in primary afferent depolarization, it exhibited periodic changes in the rhythm of efferent activity. Periodic changes of depolarization were virtually in phase in different ipsilateral segments of the lumbosacral enlargement. Data on groups of afferent fibers in whose central endings tonic and phasic changes of polarization took place. The appearance of fictitious locomotion was accompanied by a tonic increase, and of fictitious scratching by tonic inhibition of several evoked segmental responses. These tonic changes were a background against which segmental responses were modulated in step with the working rhythm of the locomotion and scratching generators. Many of the changes in evoked segmental responses were shown to be based on modulation of polarization of central endings of primary afferents by locomotion and scratching generators. It is concluded that active tonic and phase-dependent selection of incoming afferent information is effected through modulation of presynaptic inhibition of the generator. The role of this selection in peripheral collection of activity of locomotion and scratching generators is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 3, pp. 343–353, May–June, 1984.     

Pre‐/post‐otic rhombomeric interactions control the emergence of a fetal‐like respiratory rhythm in the mouse embryo

How regional patterning of the neural tube in vertebrate embryos may influence the emergence and the function of neural networks remains elusive. We have begun to address this issue in the embryonic mouse hindbrain by studying rhythmogenic properties of different neural tube segments. We have isolated pre‐ and post‐otic hindbrain segments and spinal segments of the mouse neural tube, when they form at embryonic day (E) 9, and grafted them into the same positions in stage‐matched chick hosts. Three days after grafting, in vitro recordings of the activity in the cranial nerves exiting the grafts indicate that a high frequency (HF) rhythm (order: 10 bursts/min) is generated in post‐otic segments while more anterior pre‐otic and more posterior spinal territories generate a low frequency (LF) rhythm (order: 1 burst/min). Comparison with homo‐specific grafting of corresponding chick segments points to conservation in mouse and chick of the link between the patterning of activities and the axial origin of the hindbrain segment. This HF rhythm is reminiscent of the respiratory rhythm known to appear at E15 in mice. We also report on pre‐/post‐otic interactions. The pre‐otic rhombomere 5 prevents the emergence of the HF rhythm at E12. Although the nature of the interaction with r5 remains obscure, we propose that ontogeny of fetal‐like respiratory circuits relies on: (i) a selective developmental program enforcing HF rhythm generation, already set at E9 in post‐otic segments, and (ii) trans‐segmental interactions with pre‐otic territories that may control the time when this rhythm appears. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006