Intersegmental coordinating system of the lamprey central pattern generator for locomotion

Summary In the lamprey,Ichthyomyzon unicuspis, the wave of activity required for normal swimming movements can be generated by a central pattern generator (CPG) residing in the spinal cord. A constant phase coupling between spinal segments can be organized by intersegmental coordinating neurons intrinsic to the cord. The rostral and caudal segmental oscillators of the CPG have different preferred frequencies when separated from each other. Therefore the system must maintain the segmental oscillators of the locomotor CPG at a single common frequency and with the proper relative timing. Using selective lesions and a split-bath, it is demonstrated that the coordinating system is comprised of at least 3 subsystems, short-axon systems in the lateral and medial tracts and a long axon system in the lateral tracts. Each alone can sustain relatively stable coordinated activity.Abbreviations CPG central pattern generator - NMDA N-methyl-D-aspartate - VR ventral root     

Dynamic control of the central pattern generator for locomotion

We show that an ongoing locomotor pattern can be dynamically controlled by applying discrete pulses of electrical stimulation to the central pattern generator (CPG) for locomotion. Data are presented from a pair of experiments on biological (wetware) and electrical (hardware) models of the CPG demonstrating that stimulation causes brief deviations from the CPG’s limit cycle activity. The exact characteristics of the deviation depend strongly on the phase of stimulation. Applications of this work are illustrated by examples showing how locomotion can be controlled by using a feedback loop to monitor CPG activity and applying stimuli at the appropriate times to modulate motor output. Eventually, this approach could lead to development of a neuroprosthetic device for restoring locomotion after paralysis. R. J. Vogelstein and F. Tenore contributed equally to this work.     

The nature of the coupling between segmental oscillators of the lamprey spinal generator for locomotion: A mathematical model

We present a theoretical model which is used to explain the intersegmental coordination of the neural networks responsible for generating locomotion in the isolated spinal cord of lamprey.A simplified mathematical model of a limit cycle oscillator is presented which consists of only a single dependent variable, the phase (t). By coupling N such oscillators together we are able to generate stable phase locked motions which correspond to traveling waves in the spinal cord, thus simulating fictive swimming. We are also able to generate irregular drifting motions which are compared to the experimental data obtained from cords with selective surgical lesions.     

Modular neuromuscular control of human locomotion by central pattern generator

The central pattern generators (CPG) in the spinal cord are thought to be responsible for producing the rhythmic motor patterns during rhythmic activities. For locomotor tasks, this involves much complexity, due to a redundant system of muscle actuators with a large number of highly nonlinear muscles. This study proposes a reduced neural control strategy for the CPG, based on modular organization of the co-active muscles, i.e., muscle synergies. Four synergies were extracted from the EMG data of the major leg muscles of two subjects, during two gait trials each, using non-negative matrix factorization algorithm. A Matsuoka׳s four-neuron CPG model with mutual inhibition, was utilized to generate the rhythmic activation patterns of the muscle synergies, using the hip flexion angle and foot contact force information from the sensory afferents as inputs. The model parameters were tuned using the experimental data of one gait trial, which resulted in a good fitting accuracy (RMSEs between 0.0491 and 0.1399) between the simulation and experimental synergy activations. The model׳s performance was then assessed by comparing its predictions for the activation patterns of the individual leg muscles during locomotion with the relevant EMG data. Results indicated that the characteristic features of the complex activation patterns of the muscles were well reproduced by the model for different gait trials and subjects. In general, the CPG- and muscle synergy-based model was promising in view of its simple architecture, yet extensive potentials for neuromuscular control, e.g., resolving redundancies, distributed and fast control, and modulation of locomotion by simple control signals.     

A test of a dual central pattern generator hypothesis for subcortical control of locomotion.

This study was designed to examine the nature of neural circuits involved in subcortical inter-limb coordination and reflex modulation mechanisms of locomotion. These circuits, called central pattern generators (CPGs), are believed to receive tonic input and generate rhythmically alternating sets of commands. Although CPGs have been theorized to exist in humans, their potential dual role in inter-limb coordination and reflex modulation is unclear. In the present study, nine participants walked on a treadmill, timing their heel-strikes to a metronome which varied the phase lag from 0.5 to 1.0 pi radians (0.1 pi intervals). A stimulus was delivered to the sural nerve and reflexes were measured in the ipsilateral and contralateral lower extremities through electromyography. The similarity between phase lag conditions for both temporal coordination (i.e., relative timing aspects between muscles and/or limbs) and reflex intensities suggested that they may be controlled by the same subcortical circuitry. Two plausible explanations exist: (1) a single CPG coordinates muscular contractions and phasically alters proprioceptive reflex modulation, as well as cutaneous input, using feed-forward control; (2) two separate circuits are strongly entrained, producing synchronous outputs for inter-limb coordination and reflex modulation. The out-of-phase task used in this study was limited in discerning such a difference, if it exists.     

Mathematical models for the swimming pattern of a lamprey

A significant characteristic in a swimming pattern of a lamprey is the generation of a constant phase lag along its body in spite of the wide range of undulation frequencies. In this paper, we discuss a mathematical treatment for coupled oscillators with time-delayed interaction and propose a model for the central pattern generator (CPG) of a lamprey to account for the generation of a constant phase relation, with consideration of the signal conduction time. From this model, it is suggested that the desired phase relation can be produced by long ascending connections from the tail to the neck region of the CPG.     

Central pattern generators for bipedal locomotion

Golubitsky, Stewart, Buono and Collins proposed two models for the achitecture of central pattern generators (CPGs): one for bipeds (which we call leg) and one for quadrupeds (which we call quad). In this paper we use symmetry techniques to classify the possible spatiotemporal symmetries of periodic solutions that can exist in leg (there are 10 nontrivial types) and we explore the possibility that coordinated arm/leg rhythms can be understood, on the CPG level, by a small breaking of the symmetry in quad, which leads to a third CPG architecture arm. Rhythms produced by leg correspond to the bipedal gaits of walk, run, two-legged hop, two-legged jump, skip, gallop, asymmetric hop, and one-legged hop. We show that breaking the symmetry between fore and hind limbs in quad, which yields the CPG arm, leads to periodic solution types whose associated leg rhythms correspond to seven of the eight leg gaits found in leg; the missing biped gait is the asymmetric hop. However, when arm/leg coordination rhythms are considered, we find the correct rhythms only for the biped gaits of two-legged hop, run, and gallop. In particular, the biped gait walk, along with its arm rhythms, cannot be obtained by a small breaking of symmetry of any quadruped gait supported by quad.     

A computational model of visually guided locomotion in lamprey

This study addresses mechanisms for the generation and selection of visual behaviors in anamniotes. To demonstrate the function of these mechanisms, we have constructed an experimental platform where a simulated animal swims around in a virtual environment containing visually detectable objects. The simulated animal moves as a result of simulated mechanical forces between the water and its body. The undulations of the body are generated by contraction of simulated muscles attached to realistic body components. Muscles are driven by simulated motoneurons within networks of central pattern generators. Reticulospinal neurons, which drive the spinal pattern generators, are in turn driven directly and indirectly by visuomotor centers in the brainstem. The neural networks representing visuomotor centers receive sensory input from a simplified retina. The model also includes major components of the basal ganglia, as these are hypothesized to be key components in behavior selection. We have hypothesized that sensorimotor transformation in tectum and pretectum transforms the place-coded retinal information into rate-coded turning commands in the reticulospinal neurons via a recruitment network mimicking the layered structure of tectal areas. Via engagement of the basal ganglia, the system proves to be capable of selecting among several possible responses, even if exposed to conflicting stimuli. The anatomically based structure of the control system makes it possible to disconnect different neural components, yielding concrete predictions of how animals with corresponding lesions would behave. The model confirms that the neural networks identified in the lamprey are capable of responding appropriately to simple, multiple, and conflicting stimuli.     

Hard-wired central pattern generators for quadrupedal locomotion

Animal locomotion is generated and controlled, in part, by a central pattern generator (CPG), which is an intraspinal network of neurons capable of producing rhythmic output. In the present work, it is demonstrated that a hard-wired CPG model, made up of four coupled nonlinear oscillators, can produce multiple phase-locked oscillation patterns that correspond to three common quadrupedal gaits — the walk, trot, and bound. Transitions between the different gaits are generated by varying the network's driving signal and/or by altering internal oscillator parameters. The above in numero results are obtained without changing the relative strengths or the polarities of the system's synaptic interconnections, i.e., the network maintains an invariant coupling architecture. It is also shown that the ability of the hard-wired CPG network to produce and switch between multiple gait patterns is a model-independent phenomenon, i.e., it does not depend upon the detailed dynamics of the component oscillators and/or the nature of the inter-oscillator coupling. Three different neuronal oscillator models — the Stein neuronal model, the Van der Pol oscillator, and the FitzHugh-Nagumo model -and two different coupling schemes are incorporated into the network without impeding its ability to produce the three quadrupedal gaits and the aforementioned gait transitions.     

HMGB1 is necessary for the development of lamprey

High mobility group box protein 1 (HMGB1) with a highly con-served structure in chromatin is an abundant nonhistone protein,which is involved in nucleosome fold...     

The cortex as a central pattern generator

Vertebrate spinal cord and brainstem central pattern generator (CPG) circuits share profound similarities with neocortical circuits. CPGs can produce meaningful functional output in the absence of sensory inputs. Neocortical circuits could be considered analogous to CPGs as they have rich spontaneous dynamics that, similar to CPGs, are powerfully modulated or engaged by sensory inputs, but can also generate output in their absence. We find compelling evidence for this argument at the anatomical, biophysical, developmental, dynamic and pathological levels of analysis. Although it is possible that cortical circuits are particularly plastic types of CPG ('learning CPGs'), we argue that present knowledge about CPGs is likely to foretell the basic principles of the organization and dynamic function of cortical circuits.     

On the derivation and tuning of phase oscillator models for lamprey central pattern generators

Using phase response curves and averaging theory, we derive phase oscillator models for the lamprey central pattern generator from two biophysically-based segmental models. The first one relies on network dynamics within a segment to produce the rhythm, while the second contains bursting cells. We study intersegmental coordination and show that the former class of models shows more robust behavior over the animal's range of swimming frequencies. The network-based model can also easily produce approximately constant phase lags along the spinal cord, as observed experimentally. Precise control of phase lags in the network-based model is obtained by varying the relative strengths of its six different connection types with distance in a phase model with separate coupling functions for each connection type. The phase model also describes the effect of randomized connections, accurately predicting how quickly random network-based models approach the determinisitic model as the number of connections increases.     

The stepwise development of the lamprey visual system and its evolutionary implications

Lampreys, which represent the oldest group of living vertebrates (cyclostomes), show unique eye development. The lamprey larva has only eyespot‐like immature eyes beneath a non‐transparent skin, whereas after metamorphosis, the adult has well‐developed image‐forming camera eyes. To establish a functional visual system, well‐organised visual centres as well as motor components (e.g. trunk muscles for locomotion) and interactions between them are needed. Here we review the available knowledge concerning the structure, function and development of the different parts of the lamprey visual system. The lamprey exhibits stepwise development of the visual system during its life cycle. In prolarvae and early larvae, the ‘primary’ retina does not have horizontal and amacrine cells, but does have photoreceptors, bipolar cells and ganglion cells. At this stage, the optic nerve projects mostly to the pretectum, where the dendrites of neurons in the nucleus of the medial longitudinal fasciculus (nMLF) appear to receive direct visual information and send motor outputs to the neck and trunk muscles. This simple neural circuit may generate negative phototaxis. Through the larval period, the lateral region of the retina grows again to form the ‘secondary’ retina and the topographic retinotectal projection of the optic nerve is formed, and at the same time, the extra‐ocular muscles progressively develop. During metamorphosis, horizontal and amacrine cells differentiate for the first time, and the optic tectum expands and becomes laminated. The adult lamprey then has a sophisticated visual system for image‐forming and visual decision‐making. In the adult lamprey, the thalamic pathway (retina–thalamus–cortex/pallium) also transmits visual stimuli. Because the primary, simple light‐detecting circuit in larval lamprey shares functional and developmental similarities with that of protochordates (amphioxus and tunicates), the visual development of the lamprey provides information regarding the evolutionary transition of the vertebrate visual system from the protochordate‐type to the vertebrate‐type.     

Central pattern generating networks in insect locomotion

Central pattern generators (CPGs) are neural circuits that based on their connectivity can generate rhythmic and patterned output in the absence of rhythmic external inputs. This property makes CPGs crucial elements in the generation of many kinds of rhythmic motor behaviors in insects, such as flying, walking, swimming, or crawling. Arguably representing the most diverse group of animals, insects utilize at least one of these types of locomotion during one stage of their ontogenesis. Insects have been extensively used to study the neural basis of rhythmic motor behaviors, and particularly the structure and operation of CPGs involved in locomotion. Here, we review insect locomotion with regard to flying, walking, and crawling, and we discuss the contribution of central pattern generation to these three forms of locomotion. In each case, we compare and contrast the topology and structure of the CPGs, and we point out how these factors are involved in the generation of the respective motor pattern. We focus on the importance of sensory information for establishing a functional motor output and we indicate behavior‐specific adaptations. Furthermore, we report on the mechanisms underlying coordination between different body parts. Last but not least, by reviewing the state‐of‐the‐art knowledge concerning the role of CPGs in insect locomotion, we endeavor to create a common ground, upon which future research in the field of motor control in insects can build.     

A reconsideration of the central pattern generator concept for locust flight

Summary Although it is generally agreed that locusts can generate flight similar rhythmic motor activity in the absence of sensory feedback from the wings, recent studies indicate that functional deafferentation produces significant changes in the flight motor pattern (Hedwig and Pearson 1984). These findings have raised doubts on the adequacy of the central pattern generator concept for the locust flight system (Pearson 1985). In this paper, we re-investigate the effects of deafferentation on the capacity of adult migratory locusts to generate the flight motor pattern. For this purpose, the experimental animals were dissected to various degrees, ranging from head-ventral nerve cord, to isolated pterothoracic nerve cord, and finally single isolated ganglion preparations. Flight motor activity was released by either wind stimulation, the more traditional method, or by applying octopamine (Sombati and Hoyle 1984; Stevenson and Kutsch 1986). In all cases the released motor activity was analysed, giving details of latency, and phase relationships between specific synergistic and antagonistic motor units, and then compared with the flight motor pattern generated by intact tethered locusts.This analysis shows that deafferentation, although reducing the frequency, does not necessarily disrupt the basic flight motor pattern. By using octopamine we could show that even isolated thoracic nerve cord preparations can generate activity, which in all major aspects corresponds to this motor program. This could also be shown for the fully isolated metathoracic ganglion and we provide some evidence that the mesothoracic ganglion may be capable of a similar performance. In addition to releasing flight activity, octopamine was also found to enhance the responsiveness of deafferentated locusts to wind stimulation. This resulted in a considerable elevation of the frequency and prolongation of the flight motor activity to values comparable to the performance of intact tethered locusts.     

Invertebrate central pattern generator circuits

There are now a reasonable number of invertebrate central pattern generator (CPG) circuits described in sufficient detail that a mechanistic explanation of how they work is possible. These small circuits represent the best-understood neural circuits with which to investigate how cell-to-cell synaptic connections and individual channel conductances combine to generate rhythmic and patterned output. In this review, some of the main lessons that have appeared from this analysis are discussed and concrete examples of circuits ranging from single phase to multiple phase patterns are described. While it is clear that the cellular components of any CPG are basically the same, the topology of the circuits have evolved independently to meet the particular motor requirements of each individual organism and only a few general principles of circuit operation have emerged. The principal usefulness of small systems in relation to the brain is to demonstrate in detail how cellular infrastructure can be used to generate rhythmicity and form specialized patterns in a way that may suggest how similar processes might occur in more complex systems. But some of the problems and challenges associated with applying data from invertebrate preparations to the brain are also discussed. Finally, I discuss why it is useful to have well-defined circuits with which to examine various computational models that can be validated experimentally and possibly applied to brain circuits when the details of such circuits become available.     

Crustacean motor pattern generator networks

Crustacean motor pattern-generating networks have played central roles in understanding the cellular and network bases of rhythmic motor patterns for over half a century. We review here the four best investigated of these systems: the stomatogastric, ventilatory, cardiac, and swimmeret systems. Generally applicable observations arising from this work include (1) neurons with active, endogenous cell properties (endogenous bursting, postinhibitory rebound, plateau potentials), (2) nonhierarchical (distributed) network synaptic connectivity patterns characterized by high levels of inter-neuronal connections, (3) nonspiking neurons and graded transmitter release, (4) multiple modulatory inputs, (5) networks that produce multiple patterns and have flexible boundaries, and (6) peripheral properties (proprioceptive feedback loops, low-frequency muscle filtering) playing an important role in motor pattern generation or expression.     

Numerical analysis of a unique mode of locomotion: vertical climbing by Pacific lamprey

Pacific lampreys are capable of climbing vertical wetted surfaces through a two-phase (bending and stretching) locomotion mode using the oral disc for adherence. We investigate the physical mechanism and performance of this process by using a continuous beam model. Two mechanisms, one akin to the jumping process and the other related to the fast stretching of the body, have been identified. This locomotion mode may inspire biomimetic designs of anguilliform swimming devices capable of overcoming steep obstacles. By using a genetic algorithm simulation we identify the combination of kinematic parameters corresponding to optimal efficiency (defined as the gravitational potential energy gained in each climbing step divided by the energy spent to activate the motion). These parameters are similar to laboratory observations of lamprey motion, suggesting that this type of locomotion has been optimized for maximum efficiency through evolution.