Genetic identification of spinal interneurons that coordinate left-right locomotor activity necessary for walking movements

The sequential stepping of left and right limbs is a fundamental motor behavior that underlies walking movements. This relatively simple locomotor behavior is generated by the rhythmic activity of motor neurons under the control of spinal neural networks known as central pattern generators (CPGs) that comprise multiple interneuron cell types. Little, however, is known about the identity and contribution of defined interneuronal populations to mammalian locomotor behaviors. We show a discrete subset of commissural spinal interneurons, whose fate is controlled by the activity of the homeobox gene Dbx1, has a critical role in controlling the left-right alternation of motor neurons innervating hindlimb muscles. Dbx1 mutant mice lacking these ventral interneurons exhibit an increased incidence of cobursting between left and right flexor/extensor motor neurons during drug-induced locomotion. Together, these findings identify Dbx1-dependent interneurons as key components of the spinal locomotor circuits that control stepping movements in mammals.     

Accuracy, stability, and corrective behavior in a visuomotor tracking task: a preliminary study

Visuomotor tracking tasks have been used to elucidate the underlying mechanisms that allow for the coordination of a movement to an environmental event. The main purpose of the present study was to examine the relationship between accuracy and stability of tracking performance and the amount of corrective movements that emerge for various coordination patterns in a unimanual visuomotor tracking task. Participants (N = 6) produced rhythmic elbow flexion-extension motions and were required to track an external sinusoidal signal at five different relative phases, 0°, 45°, 90°, 135°, and 180°. Differential accuracy and stability were found among the five tracking patterns with the 0° relative phase pattern being the most accurate and stable pattern. Corrective movements were correlated with changes in accuracy only for the 0° relative phase pattern, with more corrections emerging for less accurate performance. The amount of corrective movements decreased as the stability of tracking performance increased for the 0°, 45°, and 135° patterns. For the 90° and 180° tracking patterns, the amount of corrective movements was not correlated with pattern accuracy or pattern stability. The results demonstrate that corrective behaviors are an important motor process in maintaining the stability of stable perception-action coordination patterns, while offering little benefit for unstable perception-action patterns.     

Premotor interneurons in generation of adaptive leg reflexes and voluntary movements in stick insects

We investigated the role of local nonspiking interneurons involved in motor control of legs in the stick insect, Carausius morosus. In a preparation that allowed the animals to perform active leg movements such as adaptive tactile reflexes, proprioceptive reflexes, and walking, we gathered the following results. Almost all tested nonspiking interneurons that provide synaptic drive onto motoneurons of the proximal leg muscles contribute to all of the motor programs underlying tactile reflexes and voluntary leg movements such as walking, searching, and rocking. Most of them are also involved in the generation of proprioceptive reflexes. All motor programs for coactivation, avoidance reflexes, resistance reflexes, and voluntary leg movements result from parallel pathways including nonspiking interneurons that support and others that oppose the motoneuronal activity. The contribution of a single interneuron to the different motor programs is specific: it can be supporting for one motor program but opposing for the other. Even for the same motor program, for example, coactivation, the contribution of an individual interneuron can depend on the stimulus site from where the response is elicited. Our results support the idea that the different motor patterns for adaptive tactile reflexes, resistance reflexes, and voluntary leg movements emerge from a multifunctional neuronal circuit that is reorganized corresponding to the motor behavior performed. The actual motor pattern is then shaped by distributed information processing in parallel supporting and opposing pathways. © 1996 John Wiley & Sons, Inc.     

Localization of Motor Neurons and Central Pattern Generators for Motor Patterns Underlying Feeding Behavior in Drosophila Larvae

Motor systems can be functionally organized into effector organs (muscles and glands), the motor neurons, central pattern generators (CPG) and higher control centers of the brain. Using genetic and electrophysiological methods, we have begun to deconstruct the motor system driving Drosophila larval feeding behavior into its component parts. In this paper, we identify distinct clusters of motor neurons that execute head tilting, mouth hook movements, and pharyngeal pumping during larval feeding. This basic anatomical scaffold enabled the use of calcium-imaging to monitor the neural activity of motor neurons within the central nervous system (CNS) that drive food intake. Simultaneous nerve- and muscle-recordings demonstrate that the motor neurons innervate the cibarial dilator musculature (CDM) ipsi- and contra-laterally. By classical lesion experiments we localize a set of CPGs generating the neuronal pattern underlying feeding movements to the subesophageal zone (SEZ). Lesioning of higher brain centers decelerated all feeding-related motor patterns, whereas lesioning of ventral nerve cord (VNC) only affected the motor rhythm underlying pharyngeal pumping. These findings provide a basis for progressing upstream of the motor neurons to identify higher regulatory components of the feeding motor system.     

Sensory-evoked turning locomotion in red-eared turtles: kinematic analysis and electromyography

We examined the limb kinematics and motor patterns that underlie sensory-evoked turning locomotion in red-eared turtles. Intact animals were held by a band-clamp in a water-filled tank. Turn-swimming was evoked by slowly rotating turtles to the right or left via a motor connected to the shaft of the band-clamp. Animals executed sustained forward turn-swimming against the direction of the imposed rotation. We recorded video of turn-swimming and computer-analyzed the limb and head movements. In a subset of turtles, we also recorded electromyograms from identified limb muscles. Turning exhibited a stereotyped pattern of (1) coordinated forward swimming in the hindlimb and forelimb on the outer side of the turn, (2) back-paddling in the hindlimb on the inner side, (3) a nearly stationary, “braking” forelimb on the inner side, and (4) neck bending toward the direction of the turn. Reversing the rotation caused animals to switch the direction of their turns and the asymmetric pattern of right and left limb activities. Preliminary evidence suggested that vestibular inputs were sufficient to drive the behavior. Sensory-evoked turning may provide a useful experimental platform to examine the brainstem commands and spinal neural networks that underlie the activation and switching of different locomotor forms.     

Abnormal Movement Preparation in Task-Specific Focal Hand Dystonia

Electrophysiological and behavioral studies in primary dystonia suggest abnormalities during movement preparation, but this crucial phase preceding movement onset has not yet been studied specifically with functional magnetic resonance imaging (fMRI). To identify abnormalities in brain activation during movement preparation, we used event-related fMRI to analyze behaviorally unimpaired sequential finger movements in 18 patients with task-specific focal hand dystonia (FHD) and 18 healthy subjects. Patients and controls executed self-initiated or externally cued prelearnt four-digit sequential movements using either right or left hands. In FHD patients, motor performance of the sequential finger task was not associated with task-related dystonic posturing and their activation levels during motor execution were highly comparable with controls. On the other hand reduced activation was observed during movement preparation in the FHD patients in left premotor cortex / precentral gyrus for all conditions, and for self-initiation additionally in supplementary motor area, left mid-insula and anterior putamen, independent of effector side. Findings argue for abnormalities of early stages of motor control in FHD, manifesting during movement preparation. Since deficits map to regions involved in the coding of motor programs, we propose that task-specific dystonia is characterized by abnormalities during recruitment of motor programs: these do not manifest at the behavioral level during simple automated movements, however, errors in motor programs of complex movements established by extensive practice (a core feature of FHD), trigger the inappropriate movement patterns observed in task-specific dystonia.     

Kinematics and motor activity during tethered walking and turning in the cockroach, <Emphasis Type="Italic">Blaberus discoidalis</Emphasis>

When insects turn from walking straight, their legs have to follow different motor patterns. In order to examine such pattern change precisely, we stimulated single antenna of an insect, thereby initiating its turning behavior, tethered over a lightly oiled glass plate. The resulting behavior included asymmetrical movements of prothoracic and mesothoracic legs. The mesothoracic leg on the inside of the turn (in the apparent direction of turning) extended the coxa-trochanter and femur-tibia joints during swing rather than during stance as in walking, while the outside mesothoracic leg kept a slow walking pattern. Electromyograms in mesothoracic legs revealed consistent changes in the motor neuron activity controlling extension of the coxa-trochanter and femur-tibia joints. In tethered walking, depressor trochanter activity consistently preceded slow extensor tibia activity. This pattern was reversed in the inside mesothoracic leg during turning. Also for turning, extensor and depressor motor neurons of the inside legs were activated in swing phase instead of stance. Turning was also examined in free ranging animals. Although more variable, some trials resembled the pattern generated by tethered animals. The distinct inter-joint and inter-leg coordination between tethered turning and walking, therefore, provides a good model to further study the neural control of changing locomotion patterns.     

How a simple adaptive foraging strategy can lead to emergent home ranges and increased food intake

Animals often alternate between searching for food locally and moving over larger distances depending on the amount of food they find. This ability to switch between movement modes can have large implications on the fate of individuals and populations, and a mechanism that allows animals to find the optimal balance between alternative movement strategies is therefore selectively advantageous. Recent theory suggests that animals are capable of switching movement mode depending on heterogeneities in the landscape, and that different modes may predominate at different temporal scales. Here we develop a conceptual model that enables animals to use either an area‐concentrated food search behavior or undirected random movements. The model builds on the animals’ ability to remember the profitability and location of previously visited areas. In contrast to classical optimal foraging models, our model does not assume food to be distributed in large, well‐defined patches, and our focus is on animal movement rather than on how animals choose between foraging patches with known locations and value. After parameterizing the fine‐scale movements to resemble those of the harbor porpoise Phocoena phocoena we investigate whether the model is capable of producing emergent home ranges and use pattern‐oriented modeling to evaluate whether it can reproduce the large‐scale movement patterns observed for porpoises in nature. Finally we investigate whether the model enables animals to forage optimally. We found that the model was indeed able to produce either stable home ranges or movement patterns that resembled those of real porpoises. It enabled animals to maximize their food intake when fine‐tuning the memory parameters that controlled the relative contribution of area concentrated and random movements.     

Involvement of a midbrain vocal nucleus in the production of both the acoustic and postural components of crowing behavior in Japanese quail

Many bird species produce vocalizations which are accompanied by distinctive postural displays, but the neural mechanisms that allow such integrated production of vocal and postural motor patterns are not understood. In the crowing behavior of Japanese quail, a characteristic vocal pattern is accompanied by and coordinated with a postural display that consists of a sequence of rapid, patterned head movements. The purpose of the present study was to investigate the role of a midbrain vocal nucleus, the nucleus intercollicularis, in the production of the acoustic and postural components of crowing in quail. Brief electrical stimuli were applied to the nucleus intercollicularis during spontaneously emitted crows in quail with chronically implanted electrodes, to determine if perturbing neural activity in the nucleus intercollicularis resulted in a disruption of ongoing crowing behavior. The most common effect of such stimuli was a concurrent, premature termination of both the acoustic and head movement components of the crow. These results imply that the nucleus intercollicularis plays a role in the production of both the acoustic and postural components of crowing in quail.     

Control of Locomotion in a Lower Vertebrate, the Lamprey: Brainstem Command Systems and Spinal Cord Regeneration

SYNOPSIS. The lamprey, a lower vertebrate, has recently becomea very useful model system for studying motor control, includingthe organization of neural networks, and for examining the relationbetween kinematic patterns and underlying neural mechanisms.This aquatic animal displays a number of interesting locomotorbehaviors, including flexure reflexes, forward locomotion, backwardlocomotion, turning, withdrawal, and equilibrium reflexes. Avaluable property of the lamprey preparation is that the nervoussystem survives under in vitro conditions for several days andgenerates well-coordinated locomotor activity that underliessome of the above behaviors. Thus, the neural control of basiclocomotor behaviors can be studied in an isolated nervous systemin which the ionic or pharmacological make-up of the bath canbe altered and in which stable conditions are provided for intracellularrecordings. In addition, recent data indicate that the lampreypreparation is a valuable model system for studies of axonalregeneration and recovery of locomotor function following spinalcord injury. This article will focus on three aspects of locomotorbehavior in the lamprey: kinematics and motor activity of locomotorbehaviors, descending control of locomotion, and regenerationof descending brainstem command pathways that initiate locomotion.     

Predictability of visual perturbation during locomotion: implications for corrective efference copy signaling

In guiding adaptive behavior, efference copy signals or corollary discharge are traditionally considered to serve as predictors of self-generated sensory inputs and by interfering with their central processing are able to counter unwanted consequences of an animal??s own actions. Here, in a speculative reflection on this issue, we consider a different functional role for such intrinsic predictive signaling, namely in stabilizing gaze during locomotion where resultant changes in head orientation in space require online compensatory eye movements in order to prevent retinal image slip. The direct activation of extraocular motoneurons by locomotor-related efference copies offers a prospective substrate for assisting self-motion derived sensory feedback, rather than being subtracted from the sensory signal to eliminate unwanted reafferent information. However, implementing such a feed-forward mechanism would be critically dependent on an appropriate phase coupling between rhythmic propulsive movement and resultant head/visual image displacement. We used video analyzes of actual locomotor behavior and basic theoretical modeling to evaluate head motion during stable locomotion in animals as diverse as Xenopus laevis tadpoles, teleost fish and horses in order to assess the potential suitability of spinal efference copies to the stabilization of gaze during locomotion. In all three species, and therefore regardless of aquatic or terrestrial environment, the head displacements that accompanied locomotor action displayed a strong correlative spatio-temporal relationship in correspondence with a potential predictive value for compensatory eye adjustments. Although spinal central pattern generator-derived efference copies offer appropriately timed commands for extraocular motor control during self-generated motion, it is likely that precise image stabilization requires the additional contributions of sensory feedback signals. Nonetheless, the predictability of the visual consequences of stereotyped locomotion renders intrinsic efference copy signaling an appealing mechanism for offsetting these disturbances, thus questioning the exclusive role traditionally ascribed to sensory-motor transformations in stabilizing gaze during vertebrate locomotion.     

The timing of activity in motor neurons that produce radula movements distinguishes ingestion from rejection in Aplysia

1. We have studied the neural circuitry mediating ingestion and rejection in Aplysia using a reduced preparation that produces ingestion-like and rejection-like motor patterns in response to physiological stimuli.
2. We have characterized 3 buccal ganglion motor neurons that produce specific movements of the radula and buccal mass. B8a and B8b act to close the radula. B10 acts to close the jaws and retract the radula.
3. The patterns of activity in these neurons can be used to distinguish the ingestion-like and rejection-like motor patterns. B8a, B8b and B10 are active together during the ingestion-like pattern. Activity in B8a and B8b ends prior to the onset of activity in B10 during the rejection-like pattern.
4. Our data suggest that these neurons undergo similar patterns of activity in vivo. During both feeding-like patterns, the activity and peripheral actions of B8a, B8b, and B10 are consistent with radula movements observed during ingestion and rejection. In addition, the extracellular activity produced by these neurons is consistent with neural activity observed in vivo during ingestion and rejection.
5. Our data suggest that the different activity patterns observed in these motor neurons contribute to the different radula movements that distinguish ingestion from rejection.

     

On the definition of central pattern generator and its sensory control

A central pattern generator (CPG) is defined here as a neural network responsible for the production of the timing cues of a rhythmic motor output pattern in the isolated CNS. For the intact animal, model considerations show that this term is neither clearly delimited from the concept of a reflex chain nor from the concept of a pattern generator with functional principles different from those of the CPG. Therefore, it cannot be concluded from the existence of a CPG in the isolated nervous system that this CPG also provides the decisive timing cues in the intact animal. Consequences for the study of the neural basis of rhythmic movements are shown.     

The additive factor method in rat information processing

Sternberg introduced the additive factor method as a tool for discovering and studying in choice reaction time situations in human subjects. Underlying the method is the notion that if information processing consists of successive stages, then different factors affecting different stages must have additive effects on reaction-time measurements. The additive factor method has been extensively used in humans but few attempts have been made to examine whether or not additive reaction time patterns were obtainable in rats. In the present work, the subjects (13 Long–Evans rats) had to press down a lever and to respond to a visual (right or left) stimulus by releasing the lever and introducing the head into a lateral (right or left) operandum. The present findings show an additive pattern of effects of signal luminance and foreperiod duration on the mean reaction time which suggests that we have successfully manipulated two stages of rat information processing — the preprocessing stage and the motor adjustment stage, respectively. Accordingly, the present study sets the basis for the basis for investigating the effects of invasive manipulations (pharmacological and/or lesional) on information processing stages.     

Symmetry-breaking bifurcation: A possible mechanism for 2:1 frequency-locking in animal locomotion

The generation and control of animal locomotion is believed to involve central pattern generators — networks of neurons which are capable of producing oscillatory behavior. In the present work, the quadrupedal locomotor central pattern generator is modelled as four distinct but symmetrically coupled nonlinear oscillators. We show that the typical patterns for two such networks of oscillators include 2:1 frequency-locked oscillations. These patterns, which arise through symmetry-breaking Hopf bifurcation, correspond in part to observed patterns of 2:1 frequency-locking of limb movements during electrically elicited locomotion of decerebrate and spinal quadrupeds. We briefly describe how our theoretical predictions could be tested experimentally.     

Both shared and specialized spinal circuitry for scratching and swimming in turtles

In principle, nervous systems could generate a behavior either via neurons that are relatively specialized for producing one behavior or via multifunctional neurons that are shared among multiple, diverse behaviors. I recorded extracellularly from individual turtle spinal cord neurons while evoking hindlimb scratching, swimming, and withdrawal motor patterns. The majority of spinal neurons recorded were activated during both scratching and swimming motor patterns, consistent with the existence of shared circuitry for these types of limb movements. These neurons tended to have a similar degree of rhythmic modulation of their firing rate and a similar phase preference within the hip flexor activity cycle during scratching and swimming motor patterns. In addition, a substantial minority of neurons were activated during scratching motor patterns but silenced during swimming motor patterns. This raises the possibility that inhibitory interactions between some scratching and swimming neural circuitry play a role in motor pattern selection. These scratch-specialized neurons were also less likely than the putative shared neurons to be activated during withdrawal motor patterns. Thus, these neurons may represent two separate classes, one of which is used generally for hindlimb motor control and the other of which is relatively specialized for a subset of hindlimb movement types.     

Hemisphere asymmetry of motor-feeding behavior of mice in a multi-alternative symmetrical maze

The behaviour of mice of BALB/c line was studied in a symmetrical multialternative Y-maze: their motor, alimentary and investigating activities as well as spatial-motor asymmetry. In animals with inactivated left hemisphere, as compared to intact ones, the motor and alimentary activities were lowered, and the investigating one augmented. Instead of the weak left-side asymmetry a distinct left-side preference appeared of most Y-maze sections, and right-side preference for approaches to the feeders. Elimination of the right hemisphere did not change the motor activity; the alimentary one decreased and the investigating one augmented, but less than during inactivation of the left hemisphere. On the whole, the right-side asymmetry appeared for all sections. According to all parameters studied, the influence of the left hemisphere on animal behaviour was more expressive and diverse. Spatial preference is formed with participation of influences of both hemispheres. The differences between them are more qualitative than quantitative.     

Haltere and visual inputs sum linearly to predict wing (but not gaze) motor output in tethered flying Drosophila

In the true flies (Diptera), the hind wings have evolved into specialized mechanosensory organs known as halteres, which are sensitive to gyroscopic and other inertial forces. Together with the fly''s visual system, the halteres direct head and wing movements through a suite of equilibrium reflexes that are crucial to the fly''s ability to maintain stable flight. As in other animals (including humans), this presents challenges to the nervous system as equilibrium reflexes driven by the inertial sensory system must be integrated with those driven by the visual system in order to control an overlapping pool of motor outputs shared between the two of them. Here, we introduce an experimental paradigm for reproducibly altering haltere stroke kinematics and use it to quantify multisensory integration of wing and gaze equilibrium reflexes. We show that multisensory wing-steering responses reflect a linear superposition of haltere-driven and visually driven responses, but that multisensory gaze responses are not well predicted by this framework. These models, based on populations, extend also to the responses of individual flies.