Ubiquity of motor networks in the spinal cord of vertebrates

doi:10.1016/S0361-9230(00)00396-8

Brain Research Bulletin

Volume 53, Issue 5, 15 November 2000, Pages 627-634

https://doi.org/10.1016/S0361-9230(00)00396-8 Get rights and content

Abstract

In a recent paper, we found that it is possible to record motor activity in sacral segments in the in vitro neonatal rat spinal cord preparation. This motor activity recorded in segments that are not innervating hindlimbs is driven by the lumbar locomotor network. Indeed, compartimentalizations of the cord with Vaseline walls or section experiments, reveals that the sacral segments possess their own rhythmogenic capabilities but that in an intact spinal cord they are driven by the lumbar locomotor network. In this review, these recent findings are placed in the context of spinal motor network interactions. As previously suspected, the motor networks do not operate in isolation but interact with each other according to behavioural needs. These interactions provide some insight into the discrepancies observed in several studies dealing with the localization of the lumbar locomotor network in the neonatal rat spinal cord. In conclusion, the spinal cord of quadrupeds appears as an heterogeneous structure where it is possible to identify neuronal networks that are crucial for the genesis of locomotor-related activities.

Introduction

Most animals need to move to find food, sexual partners and to escape from predators. This necessity for movement led to the establishment, during evolution, of several locomotor strategies adapted to the life medium of the animals. In vertebrates, such as fishes or snakes, propulsion is sustained by rhythmic undulatory trunk movements while bipeds or quadrupeds locomote using rhythmic coordinated movements of the limbs. Some “transitional” organisms, as for example the newt, can adopt either locomotor strategy depending on the medium. In terrestrial mammals, it appears that the biomechanical processes underlying locomotion can not solely be described by alternating limb movements but also require complex coordinated trunk movements and postural regulation. The neuronal basis for these various kinds of rhythmic motor behaviours have been studied throughout the vertebrate phylum. An understanding that the motor patterns are centrally generated in the spinal cord by specific neuronal networks called central pattern generators (CPGs) has emerged.

The motor patterns generated by the spinal cord are varied and extend from phrenic bursts to limb movements. The aim of this review is to focus on locomotion-related networks and to describe the interactions between such neuronal assemblies. Special attention will be given to results obtained in the in vitro neonatal rat spinal cord preparation.

Section snippets

Different forms of rhythmic motor activities generated in the spinal cord

Two kinds of rhythmic motor patterns are generated by the spinal cord. First, there are motor patterns such as controlling forelimb and hindlimb movements (for review see [34]), swimming 33, 44, flying [54], hatching (for review see [3]), scratching, paw-shake [62] (for a review on scratching and paw-shake see [57]), and trunk muscle movements [31]. This is not an exhaustive list but includes the more commonly studied motor behaviours. Second, there are postural patterns which are under strong

The neonatal rat spinal cord preparation

Before describing the coupling between neuronal networks, we will briefly introduce the neonatal rat spinal cord preparation (Fig. 1A), which allows us to study these various motor networks under isolating conditions. Over the last 10 years, the isolated spinal cord of the neonatal rat has been used to study both the developmental aspects and the cellular bases of locomotor activity. In this preparation, locomotor like activity can be elicited by bath-application of various neurotransmitters

Interactions between spinal motor networks

Distinct neuronal networks are thought to underlie different motor activities. The networks that subserve these various motor activities, however, do not normally operate in isolation but interact with each other, according to behavioural needs. Interactions within the spinal cord are probably complex and to date, little information is available concerning the coupling between the different motor networks.

Generation of motor pattern by specialized networks

The spinal cord consists of multiple networks each of them with its own specificity, that can share neuronal elements. Virtually all spinal levels are susceptible to exhibit rhythmic activation and the various neuronal networks will be active according to their particular and specific properties during motor tasks. The question that arises is to know if all spinal segments in the cord possess the same capabilities to generate motor patterns or if some contain key elements for one type of motor

Conclusion

Various findings indicate that the spinal cord in quadrupeds is not an homogeneous chain of equipotent networks, as it is the case for example in organisms which exhibit an anguilliform swimming such as lamprey 32, 33. On one side one should consider the activity recorded at the segmental level for back muscle activity along the axis of the body and. On the other side more specialized areas corresponding to hindlimbs will largely influence the functioning of the trunk muscles. As revealed by

Acknowledgements

The authors warmly thank Dr. C. E. Gee for critical reading of the manuscript and correcting the language.

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These neurons are the Pitx2+ and acetylcholinergic neurons, called V0C, since they are derived from the V0 population. V0C neurons are shown to be the exclusive source of the well-known large acetylcholinergic C-boutons that were first discovered on motor neurons more than 40 years ago [66]. The V0C neurons are rhythmically active during locomotor-like activity and genetic inactivation of these cells reduces the amplitude of the locomotor output in a task-dependent way [26].
Locomotion in mammals is a complex motor act that involves the activation of a large number of muscles in a well-coordinated pattern. Understanding the network organization of the intrinsic spinal networks that control the locomotion, the central pattern generators, has been a challenge to neuroscientists. However, experiments using the isolated rodent spinal cord and combining electrophysiology and molecular genetics to dissect the locomotor network have started to shed new light on the network structure. In the present review, we will discuss findings that have revealed the role of designated populations of neurons for the key network functions including coordinating muscle activity and generating rhythmic activity. These findings are summarized in proposed organizational principles for the mammalian segmental CPG.
Distributed neural networks for controlling human locomotion. Lessons from normal and SCI subjects
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However, opinions diverge as to whether the mammalian CPGs are localized or distributed [49,64], and the details of such circuitry in the human spinal cord are still largely unknown [8,17,22,28,51,59,83]. A major site for CPG activity in the upper lumbar segments may serve a pace-maker role, together with other, perhaps separate generator sites in more caudal segments [9,50,55]. The cervical segments of the cord also contain pattern-generating oscillators for coordinating the upper limbs.
The control of human locomotion engages various brain structures and numerous muscles. Even though the hypothetical central pattern generator (CPG) and sensory feedback can sustain the basic locomotor rhythm, the resultant motor output is highly adaptable and context-dependent. Indeed, while the temporal architecture of the locomotor output (basic EMG components) is relatively conserved across subjects and conditions, the spatial architecture (muscle activations) shows considerable non-linear changes with walking speed, level of body unloading or the direction of progression. Even so, leg kinematics are remarkably similar in all cases. Spinal cord injured (SCI) patients may learn new motor patterns with training rather than re-activate normal motor patterns, and such locomotor improvements may not transfer to untrained tasks. Redundancy in the neuromuscular system or malfunctioning of injured ‘elements’ may often result in motor equivalent compensatory solutions. Injured pathways can partially recover while uninjured pathways can augment or modify their activity. As a result, the reconstructed spatiotemporal maps of motor neuron activity in SCI patients might be quite different from those of healthy subjects but they nevertheless achieve nearly normal foot kinematics. Kinematics training may thus provide a more successful rehabilitation than training based on reconstructing normal muscle activation patterns. Taken together, recent data support the idea of plasticity and distributed networks for controlling human locomotion. A new generation of robotic devices takes advantage of this by providing the opportunity for patients to generate and correct limb movements rather than just adapting muscle activation to the fixed kinematic template imposed by a gait orthosis.
Plasticity properties of CPG circuits in humans: Impact on gait recovery
2009, Brain Research Bulletin
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Numerous evidence in experimental models as well as in humans indicates that CPG circuits are indeed innate. On the other hand, controversy exist on the exact location of the CPG circuits and recent research in humans [16,38] and in animal models [4,6] indicated that spinal CPG circuits may not be localized but distributed throughout the spinal cord (see also Ivanenko, this issue). This lack of precise localization of CPG properties, at least in the spinal cord, question what is innate in CPG circuits.
Recent data on spinal cord plasticity after spinal cord injury (SCI) emphasize the influence of training on determining the functional organization of the spinal circuits that provide the appropriate sequence and intensity of muscular activation needed for gait the so-called central pattern generator (CPG) circuits. This evidence questions the essence of CPG circuits. Are the CPG characteristics innate or are they induced in spinal cord neurons by training? The answer of this question present obvious consequences on the rehabilitative approach to spinal cord injury patients. After briefly reviewing present knowledge on the anatomical and functional organization of spinal CPG in animal models of SCI, data on humans are presented. Evidence indicating that, after SCI, specific functional properties of gait CPG can be induced de novo by specific training in spinal neurons are reported and the hypothesis that CPG circuits may be determined by experience is advanced.
Coordinated network functioning in the spinal cord: An evolutionary perspective
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Citation Excerpt :
Based on behavioural experiments first performed on neonatal rats during swimming, where a strong coordination exists between fore- and hindlimb EMG rhythmic activities (Cazalets et al., 1990), the spinal localisation of the forelimb locomotor generators was later investigated in spinal cord preparations in vitro. When chemically activated by neuroactive agents such as NMA and serotonin (Fig. 4B), rhythmic ventral root activity was found to be generated at the cervical (C8) level of the cord and in an in-phase coordination with homolateral lumbar (L5) output, similar to that observed in the freely moving animal (Cazalets and Bertrand, 2000b; Juvin et al., 2005). Using a partitioned spinal cord preparation that restricts the superfusion of NMDA/5-HT to the cervico-thoracic levels, synchronous bursting was found to occur in homolateral C7 to T1 ventral roots (extensor motoneurons), and an alternation with both the contralateral side of the cord and homolateral C3–C5 roots (flexor motoneurons, Fig. 4B, Ballion et al., 2001).
The successful achievement of harmonious locomotor movement results from the integrated operation of all body segments. Here, we will review current knowledge on the functional organization of spinal networks involved in mammalian locomotion. Attention will not simply be restricted to hindlimb muscle control, but by also considering the necessarily coordinated activation of trunk and forelimb muscles, we will try to demonstrate that while there has been a progressive increase in locomotor system complexity during evolution, many basic organizational features have been preserved across the spectrum from lower vertebrates through to humans. Concerning the organization of axial neuronal networks that control trunk muscles, it has been found across the vertebrate range that during locomotor movement a motor wave travels longitudinally in the spinal cord via the coupling of rhythmic segmental networks. For hindlimb activation it has been found in all species studied that the rostral lumbar segments contain the key elements for pattern generation. We also showed that rhythmic arm movements are under the control of cervical forelimb generators in quadrupeds as well as in human. Finally, it is highlighted that the coordination of quadrupedal movements during locomotion derives principally from an asymmetrical coordinating influence occurring in the caudo-rostral direction from the lumbar hindlimb networks.
The early development of motor control in neonate rat
2006, Comptes Rendus - Palevol
Citation Excerpt :
The coordinated firing of the motoneurons controlling these muscles is organised at the level of the spinal cord by neural networks, called central pattern generators (CPG) [68]. A rostral CPG, located between C7-T1, controls the fore limbs [3], and a lumbar CPG, located between L1–L5 controls the hind limbs [13,14,36]. CPGs are made of two lateral hemi-neural networks, that rhythmically stimulate a pool of motoneurons through glutamatergic synapses and inhibit the motoneurons of the ipsilateral antagonist muscles and the contralateral agonist muscles through glycinergic commissural interneurons (see [26] for a recent review).
Neonates of altricial species show reduced motor performances with reference to precocial species. Supposedly, their unachieved motor output mirrors the poorly matured underlying structures. Reviewing the developmental timetable of neural, motor and postural structures involved in rats' walking shows that fundamental elements for a basic locomotion are present early after birth, whereas late developing structures are implied in complex behaviours. Whereas rat pups spontaneously show limited motor properties, they can reveal better motor capacities in particular behavioural situations. It is proposed that motor output spontaneously performed by pups does not mirror the actual properties of the motor structures, but results also from a selected behavioural mechanism whose function is to maintain the pups to the nest. To cite this article: M. Jamon, C. R. Palevol 5 (2006).
Le développement précoce du contrôle moteur chez le rat nouveau-né. Les nouveau-nés des espèces nidicoles ont des performances motrices retardées par rapport aux espèces nidifuges. Ces performances réduites sont supposées refléter le caractère inachevé des structures impliquées dans la motricité. L'analyse du développement des structures neuronales, motrices et posturales montre que les éléments fondamentaux pour une motricité rudimentaire sont présents tôt après la naissance. Le développement plus tardif concerne des structures impliquées dans des comportements plus complexes. Les ratons montrent spontanément des comportements moteurs limités, mais révèlent des capacités motrices plus performantes dans des situations expérimentales particulières. On propose ici que les habilités motrices exprimées spontanément ne représentent pas les propriétés réelles des structures motrices, mais répondent plutôt à des comportements sélectionnés pour maintenir le raton dans le nid. Pour citer cet article : M. Jamon, C. R. Palevol 5 (2006).
Physiological, anatomical and genetic identification of CPG neurons in the developing mammalian spinal cord
2003, Progress in Neurobiology
The basic motor patterns underlying rhythmic limb movements during locomotion are generated by neuronal networks located within the spinal cord. These networks are called Central Pattern Generators (CPGs). Isolated spinal cord preparations from newborn rats and mice have become increasingly important for understanding the organization of the CPG in the mammalian spinal cord. Early studies using these preparations have focused on the overall network structure and the localization of the CPG. In this review we concentrate on recent experiments aimed at identifying and characterizing CPG-interneurons in the rodent. These experiments include the organization and function of descending commissural interneurons (dCINs) in the hindlimb CPG of the neonatal rat, as well as the role of Ephrin receptor A4 (EphA4) and its Ephrin ligand B3 (EphrinB3), in the construction of the mammalian locomotor network. These latter experiments have defined EphA4 as a molecular marker for mammalian excitatory hindlimb CPG neurons. We also review genetic approaches that can be applied to the mouse spinal cord. These include methods for identifying sub-populations of neurons by genetically encoded reporters, techniques to trace network connectivity with cell-specific genetically encoded tracers, and ways to selectively ablate or eliminate neuron populations from the CPG. We propose that by applying a multidisciplinary approach it will be possible to understand the network structure of the mammalian locomotor CPG. Such an understanding will be instrumental in devising new therapeutic strategies for patients with spinal cord injury.

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^†: Present address: Université de Montréal, Dépt de Physiologie, CP 6128, succ. Centre Ville H3C 3J7 Montréal, Quebec, Canada.

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Ubiquity of motor networks in the spinal cord of vertebrates

Abstract

Introduction

Section snippets

Different forms of rhythmic motor activities generated in the spinal cord

The neonatal rat spinal cord preparation

Interactions between spinal motor networks

Generation of motor pattern by specialized networks

Conclusion

Acknowledgements

Brain Res.

Dev. Brain Res.

Brain Res.

Behav. Brain Res.

Brain Res. Dev. Brain Res.

Neuron

Trends Neurosci.

Neurosci. Lett.

Neurosci. Lett.

Brain Res.

Prog. Neurobiol.

Brain Res.

Prog. Brain Res.

J. Neurosci. Methods

Brain Res.

Brain Res.

J. Physiol. (Paris)

Brain Res.

Control of locomotion in vitroII. Chemical stimulation

Somatosens. Mot. Res.

Interaction between disinhibited bursting and fictive locomotor patterns in the rat isolated spinal cord

J. Neurophysiol.

Neuroethological approaches to the study of motor development in chicksAchievements and challenges

J. Neurobiol.

Neural control of hatchingFate of the pattern generator for the leg movements of hatching in post-hatching chicks

J. Neurosci.

Spontaneous rhythmic bursts induced by pharmacological block of inhibition in lumbar motoneurons of the neonatal rat spinal cord

J. Neurophysiol.

Localization of rhythmogenic networks responsible for spontaneous bursts induced by strychnine and bicuculline in the rat isolated spinal cord

J. Neurosci.

Control of the trunk during walking in the cat

Acta Physiol. Scand.

Organization of the spinal locomotor network in neonatal rat

Coupling between lumbar and sacral motor networks in the neonatal rat spinal cord

Eur. J. Neurosci.

Activation of the central pattern generators for locomotion by serotonin and excitatory amino acids in neonatal rat

J. Physiol.

Localization and organization of the central pattern generator for hindlimb locomotion in newborn rat

J. Neurosci.

Identification, localization, and modulation of neural networks for walking in the mudpuppy (Necturus maculatus) spinal cord

J. Neurosci.

Regional distribution of the locomotor pattern-generating network in the neonatal rat spinal cord

J. Neurophysiol.

Experimentally derived model for the locomotor pattern generator in the Xenopus embryo

J. Physiol.

Central neuronal circuit innervating the lordosis-producing muscles defined by transneuronal transport of pseudorabies virus

J. Neurosci.

Effect of bicuculline on thalamic activityA direct blockade of IAHP in reticularis neurons

J. Neurophysiol.

Efferent activity during fictitious scratch reflex in the cat

J. Neurophysiol.

Fictive rhythmic motor patterns induced by NMDA in an in vitro brain stem-spinal cord preparation from an adult urodele

J. Neurophysiol.

Epaxial and limb muscle activity during swimming and terrestrial stepping in the adult newt, Pleurodeles waltl

J. Neurophysiol.