scholarly journals Recent Insights into the Rhythmogenic Core of the Locomotor CPG

2021 ◽  
Vol 22 (3) ◽  
pp. 1394
Author(s):  
Vladimir Rancic ◽  
Simon Gosgnach
Keyword(s):  
Neural Network ◽  
Spinal Cord ◽  
Muscle Activation ◽  
Central Pattern Generators ◽  
Cell Types ◽  
Genetic Approach ◽  
Spinal Neurons ◽  
Locomotor Rhythm ◽  
Key Features ◽  
Pattern Generators

In order for locomotion to occur, a complex pattern of muscle activation is required. For more than a century, it has been known that the timing and pattern of stepping movements in mammals are generated by neural networks known as central pattern generators (CPGs), which comprise multiple interneuron cell types located entirely within the spinal cord. A genetic approach has recently been successful in identifying several populations of spinal neurons that make up this neural network, as well as the specific role they play during stepping. In spite of this progress, the identity of the neurons responsible for generating the locomotor rhythm and the manner in which they are interconnected have yet to be deciphered. In this review, we summarize key features considered to be expressed by locomotor rhythm-generating neurons and describe the different genetically defined classes of interneurons which have been proposed to be involved.

Mechanosensory inputs to the central pattern generators for locomotion in the lamprey spinal cord: resetting, entrainment, and computer modeling

1993 ◽  
Vol 70 (6) ◽  
pp. 2442-2454 ◽  
Author(s):  
A. D. McClellan ◽  
W. Jang
Keyword(s):  
Spinal Cord ◽  
Cycle Time ◽  
Central Pattern Generators ◽  
Phase Delay ◽  
Phase Advance ◽  
Response Curves ◽  
Locomotor Rhythm ◽  
Cycle Times ◽  
Pattern Generators

1. Mechanoreceptors in the lamprey spinal cord have inputs to the central pattern generator (CPG) for locomotion. In the present study, imposed sinusoidal and pulsed movements were applied to the end of the in vitro lamprey spinal cord to excite the mechanoreceptors so that the relationship between entrainment and resetting of the locomotor rhythm could be examined. 2. The range over which the locomotor rhythm could be entrained by sinusoidal movements was asymmetric and occurred mostly at movement cycle times below the resting cycle time. During entrainment at the shortest cycle times, the movement phases were relatively small. 3. The phase response curves (PRCs) displayed the greatest shortening of cycle times (phase advance) for movement pulses applied during the first half of the locomotor cycle, whereas movement pulses applied during the second half of the cycle were largely ineffective. The amplitude of phase shifts in the PRC correlated with the ranges of cycle times over which entrainment occurred. 4. During resetting from movement pulses applied early in the cycle, the burst and interburst parts of the cycle shortened by about the same percentage. In addition, resetting effects occurred simultaneously along the spinal cord, suggesting a rapid distribution of timing information. 5. A computer model of the CPGs, consisting of left and right oscillators and inputs from mechanosensory elements, produced entrainment ranges that were symmetric around the resting cycle time. The PRCs from the model showed phase advance for movement pulses applied during the first half of the cycle and phase delay for pulses applied during the second half of the cycle. 6. Because of the asymmetric experimental PRCs for the lamprey spinal cord, gating was incorporated into the cooffter model such that oscillators on one side of the model gated inputs from mechanosensory elements on the same side. With gating, the model produced entrainment ranges that were asymmetric and confined to cycle times below the resting cycle time. The PRCs still showed phase advance for pulses applied at the beginning of the cycle, and the amount of phase delay produced during the second half of the cycle was substantially reduced compared with the simulations without gating.

scholarly journals Understanding axial progenitor biology in vivo and in vitro

Development ◽  
2021 ◽  
Vol 148 (4) ◽  
pp. dev180612
Author(s):  
Filip J. Wymeersch ◽  
Valerie Wilson ◽  
Anestis Tsakiridis
Keyword(s):  
Spinal Cord ◽  
Vertebral Column ◽  
Cell Types ◽  
Disease Modelling ◽  
Recent Developments ◽  
The Common ◽  
Key Features ◽  
Trunk Musculature

ABSTRACTThe generation of the components that make up the embryonic body axis, such as the spinal cord and vertebral column, takes place in an anterior-to-posterior (head-to-tail) direction. This process is driven by the coordinated production of various cell types from a pool of posteriorly-located axial progenitors. Here, we review the key features of this process and the biology of axial progenitors, including neuromesodermal progenitors, the common precursors of the spinal cord and trunk musculature. We discuss recent developments in the in vitro production of axial progenitors and their potential implications in disease modelling and regenerative medicine.

scholarly journals Trpm5 channels encode bistability of spinal motoneurons and ensure motor control of hindlimbs in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rémi Bos ◽  
Benoît Drouillas ◽  
Mouloud Bouhadfane ◽  
Emilie Pecchi ◽  
Virginie Trouplin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Endoplasmic Reticulum ◽  
Molecular Mechanisms ◽  
Central Pattern Generators ◽  
Cellular Level ◽  
Spinal Motoneurons ◽  
Plateau Potential ◽  
Serca Pump ◽  
Pattern Generators ◽  
Postural Tone

AbstractBistable motoneurons of the spinal cord exhibit warmth-activated plateau potential driven by Na+ and triggered by a brief excitation. The thermoregulating molecular mechanisms of bistability and their role in motor functions remain unknown. Here, we identify thermosensitive Na+-permeable Trpm5 channels as the main molecular players for bistability in mouse motoneurons. Pharmacological, genetic or computational inhibition of Trpm5 occlude bistable-related properties (slow afterdepolarization, windup, plateau potentials) and reduce spinal locomotor outputs while central pattern generators for locomotion operate normally. At cellular level, Trpm5 is activated by a ryanodine-mediated Ca2+ release and turned off by Ca2+ reuptake through the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump. Mice in which Trpm5 is genetically silenced in most lumbar motoneurons develop hindlimb paresis and show difficulties in executing high-demanding locomotor tasks. Overall, by encoding bistability in motoneurons, Trpm5 appears indispensable for producing a postural tone in hindlimbs and amplifying the locomotor output.

scholarly journals Modulation of motoneurone excitability during rhythmic motor outputs

2018 ◽  
Vol 43 (11) ◽  
pp. 1176-1185 ◽  
Author(s):  
Kevin E. Power ◽  
Evan J. Lockyer ◽  
Davis A. Forman ◽  
Duane C. Button
Keyword(s):  
Spinal Cord ◽  
Electrical Properties ◽  
Central Pattern Generators ◽  
Indirect Evidence ◽  
Rhythmic Motor ◽  
Current State ◽  
Motor Outputs ◽  
Descending Input ◽  
Pattern Generators ◽  
Spinal Motoneurones

In quadrupeds, special circuity located within the spinal cord, referred to as central pattern generators (CPGs), is capable of producing complex patterns of activity such as locomotion in the absence of descending input. During these motor outputs, the electrical properties of spinal motoneurones are modulated such that the motoneurone is more easily activated. Indirect evidence suggests that like quadrupeds, humans also have spinally located CPGs capable of producing locomotor outputs, albeit descending input is considered to be of greater importance. Whether motoneurone properties are reconfigured in a similar manner to those of quadrupeds is unclear. The purpose of this review is to summarize our current state of knowledge regarding the modulation of motoneurone excitability during CPG-mediated motor outputs using animal models. This will be followed by more recent work initially aimed at understanding changes in motoneurone excitability during CPG-mediated motor outputs in humans, which quickly expanded to also include supraspinal excitability.

scholarly journals Functionally distinct Purkinje cell types show temporal precision in encoding locomotion

2020 ◽  
Vol 117 (29) ◽  
pp. 17330-17337
Author(s):  
Weipang Chang ◽  
Andrea Pedroni ◽  
Victoria Hohendorf ◽  
Stefania Giacomello ◽  
Masahiko Hibi ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Central Pattern Generators ◽  
Cell Types ◽  
Neuronal Population ◽  
Adult Zebrafish ◽  
Temporal Precision ◽  
Distinct Cell ◽  
Pattern Generators ◽  
Cell Networks

Purkinje cells, the principal neurons of cerebellar computations, are believed to comprise a uniform neuronal population of cells, each with similar functional properties. Here, we show an undiscovered heterogeneity of adult zebrafish Purkinje cells, revealing the existence of anatomically and functionally distinct cell types. Dual patch-clamp recordings showed that the cerebellar circuit contains all Purkinje cell types that cross-communicate extensively using chemical and electrical synapses. Further activation of spinal central pattern generators (CPGs) revealed unique phase-locked activity from each Purkinje cell type during the locomotor cycle. Thus, we show intricately organized Purkinje cell networks in the adult zebrafish cerebellum that encode the locomotion rhythm differentially, and we suggest that these organizational properties may also apply to other cerebellar functions.

scholarly journals Central pattern generators in the turtle spinal cord: selection among the forms of motor behaviors

2018 ◽  
Vol 119 (2) ◽  
pp. 422-440 ◽  
Author(s):  
Paul S. G. Stein
Keyword(s):  
Spinal Cord ◽  
Motor Pattern ◽  
Central Pattern Generators ◽  
Knee Extensor ◽  
Motor Patterns ◽  
Motor Behaviors ◽  
Multiple Behaviors ◽  
Pattern Generators ◽  
Electrical Stimuli

Neuronal networks in the turtle spinal cord have considerable computational complexity even in the absence of connections with supraspinal structures. These networks contain central pattern generators (CPGs) for each of several behaviors, including three forms of scratch, two forms of swim, and one form of flexion reflex. Each behavior is activated by a specific set of cutaneous or electrical stimuli. The process of selection among behaviors within the spinal cord has multisecond memories of specific motor patterns. Some spinal cord interneurons are partially shared among several CPGs, whereas other interneurons are active during only one type of behavior. Partial sharing is a proposed mechanism that contributes to the ability of the spinal cord to generate motor pattern blends with characteristics of multiple behaviors. Variations of motor patterns, termed deletions, assist in characterization of the organization of the pattern-generating components of CPGs. Single-neuron recordings during both normal and deletion motor patterns provide support for a CPG organizational structure with unit burst generators (UBGs) whose members serve a direction of a specific degree of freedom of the hindlimb, e.g., the hip-flexor UBG, the hip-extensor UBG, the knee-flexor UBG, the knee-extensor UBG, etc. The classic half-center hypothesis that includes all the hindlimb flexors in a single flexor half-center and all the hindlimb extensors in a single extensor half-center lacks the organizational complexity to account for the motor patterns produced by turtle spinal CPGs. Thus the turtle spinal cord is a valuable model system for studies of mechanisms responsible for selection and generation of motor behaviors. NEW & NOTEWORTHY The concept of the central pattern generator (CPG) is a major tenet in motor neuroethology that has influenced the design and interpretations of experiments for over a half century. This review concentrates on the turtle spinal cord and describes studies from the 1970s to the present responsible for key developments in understanding the CPG mechanisms responsible for the selection and production of coordinated motor patterns during turtle hindlimb motor behaviors.

Central pattern generators in the brainstem and spinal cord: an overview of basic principles, similarities and differences

2019 ◽  
Vol 30 (2) ◽  
pp. 107-164 ◽  
Author(s):  
Inge Steuer ◽  
Pierre A. Guertin
Keyword(s):  
Spinal Cord ◽  
Animal Models ◽  
Central Pattern Generators ◽  
Basic Principles ◽  
Advanced Level ◽  
Motor Behaviors ◽  
Similarities And Differences ◽  
Pattern Generators

AbstractCentral pattern generators (CPGs) are generally defined as networks of neurons capable of enabling the production of central commands, specifically controlling stereotyped, rhythmic motor behaviors. Several CPGs localized in brainstem and spinal cord areas have been shown to underlie the expression of complex behaviors such as deglutition, mastication, respiration, defecation, micturition, ejaculation, and locomotion. Their pivotal roles have clearly been demonstrated although their organization and cellular properties remain incompletely characterized. In recent years, insightful findings about CPGs have been made mainly because (1) several complementary animal models were developed; (2) these models enabled a wide variety of techniques to be used and, hence, a plethora of characteristics to be discovered; and (3) organizations, functions, and cell properties across all models and species studied thus far were generally found to be well-preserved phylogenetically. This article aims at providing an overview for non-experts of the most important findings made on CPGs inin vivoanimal models,in vitropreparations from invertebrate and vertebrate species as well as in primates. Data about CPG functions, adaptation, organization, and cellular properties will be summarized with a special attention paid to the network for locomotion given its advanced level of characterization compared with some of the other CPGs. Similarities and differences between these networks will also be highlighted.

The Human Central Pattern Generator for Locomotion: Does It Exist and Contribute to Walking?

2017 ◽  
Vol 23 (6) ◽  
pp. 649-663 ◽  
Author(s):  
Karen Minassian ◽  
Ursula S. Hofstoetter ◽  
Florin Dzeladini ◽  
Pierre A. Guertin ◽  
Auke Ijspeert
Keyword(s):  
Spinal Cord ◽  
Neural Control ◽  
Muscle Activation ◽  
Central Pattern Generators ◽  
Lumbar Spinal Cord ◽  
Step Cycle ◽  
Experimental Conditions ◽  
Activation Patterns ◽  
Muscle Activation Patterns ◽  
Cord Injury

The ability of dedicated spinal circuits, referred to as central pattern generators (CPGs), to produce the basic rhythm and neural activation patterns underlying locomotion can be demonstrated under specific experimental conditions in reduced animal preparations. The existence of CPGs in humans is a matter of debate. Equally elusive is the contribution of CPGs to normal bipedal locomotion. To address these points, we focus on human studies that utilized spinal cord stimulation or pharmacological neuromodulation to generate rhythmic activity in individuals with spinal cord injury, and on neuromechanical modeling of human locomotion. In the absence of volitional motor control and step-specific sensory feedback, the human lumbar spinal cord can produce rhythmic muscle activation patterns that closely resemble CPG-induced neural activity of the isolated animal spinal cord. In this sense, CPGs in humans can be defined by the activity they produce. During normal locomotion, CPGs could contribute to the activation patterns during specific phases of the step cycle and simplify supraspinal control of step cycle frequency as a feedforward component to achieve a targeted speed. Determining how the human CPGs operate will be essential to advance the theory of neural control of locomotion and develop new locomotor neurorehabilitation paradigms.

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