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Monoaminergic and catecholaminergic activation of the central pattern generator for locomotion following spinal cord injury Innovative therapeutic approaches

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Neural Regeneration Research 2009年第10期4卷 796-800页

作者： Pierre A.Guertin Neuroscience Unit Laval University Medical Center(CHUL-CHUQ) Faculty of Medicine Department of Anatomy and PhysiologyLaval University

The development of secondary health complications following spinal cord injury has been increasingly recognized by healthcare professionals as a major concern. These problems most specifically affect complete or near-complete spinal cord injury patients （e.g., those with minimal mobility）, who are not typically rehabilitated with treadmill training approaches, because motor control and leg movements are largely impaired. However, recent pharmaceutical advances in central pattern generator activation may provide new therapeutic hopes for these spinal cord injury patients. This article provides a comprehensive overview, for the non-specialist, of the most recent advances in this field.

关键词： central pattern generator locomotion spinal cord injury mice

Chx10+V2a interneurons in spinal motor regulation and spinal cord injury

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Neural Regeneration Research 2023年第5期18卷 933-939页

作者： Wen-Yuan Li Ling-Xiao Deng Feng-Guo Zhai Xiao-Yu Wang Zhi-Gang Li Ying Wang Institute of Neural Tissue Engineering Mudanjiang College of MedicineMudanjiangHeilongjiang ProvinceChina Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteIndiana University School of MedicineIndianapolisINUSA Department of Pharmacy Mudanjiang College of MedicineMudanjiangHeilongjiang ProvinceChina Department of General Surgery Hongqi HospitalMudanjiang College of MedicineMudanjiangHeilongjiang ProvinceChina

Chx10-expressing V2 a(Chx10+V2 a) spinal interneurons play a large role in the excitatory drive of motoneurons. Chemogenetic ablation studies have demonstrated the essential nature of Chx10+V2 a interneurons in the regulation of locomotor initiation, maintenance, alternation, speed, and rhythmicity. The role of Chx10+V2 a interneurons in locomotion and autonomic nervous system regulation is thought to be robust, but their precise role in spinal motor regulation and spinal cord injury have not been fully explored. The present paper reviews the origin, characteristics, and functional roles of Chx10+V2 a interneurons with an emphasis on their involvement in the pathogenesis of spinal cord injury. The diverse functional properties of these cells have only been substantiated by and are due in large part to their integration in a variety of diverse spinal circuits. Chx10+V2 a interneurons play an integral role in conferring locomotion, which integrates various corticospinal, mechanosensory, and interneuron pathways. Moreover, accumulating evidence suggests that Chx10+V2 a interneurons also play an important role in rhythmic patterning maintenance, leftright alternation of central pattern generation, and locomotor pattern generation in higher order mammals, likely conferring complex locomotion. Consequently, the latest research has focused on postinjury transplantation and noninvasive stimulation of Chx10+V2 a interneurons as a therapeutic strategy, particularly in spinal cord injury. Finally, we review the latest preclinical study advances in laboratory derivation and stimulation/transplantation of these cells as a strategy for the treatment of spinal cord injury. The evidence supports that the Chx10+V2 a interneurons act as a new therapeutic target for spinal cord injury. Future optimization strategies should focus on the viability, maturity, and functional integration of Chx10+V2 a interneurons transplanted in spinal cord injury foci.

关键词： axons central nervous system central pattern generator Chx10 differentiation interneurons locomotion motor neurons propriospinal spinal cord injuries therapy transcription factor transplantation V2a neuron

Semaphorin7A:its role in the control of serotonergic circuits and functional recovery following spinal cord injury

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Neural Regeneration Research 2022年第5期17卷 959-962页

作者： Julie Fourneau Florence M.Bareyre Institute of Clinical Neuroimmunology Ludwig-Maximilians Universität MünchenMunichGermany Munich Cluster of Systems Neurology(SyNergy) MunichGermany

Serotonin is a monoamine neurotransmitter synthetized in various populations of brainstem neurons.In the spinal cord,descending serotonergic projections regulate postural muscle tone,locomotion and rhythm and coordination of movements via the central pattern generator.Following a spinal cord injury,serotonergic projections to the lumbar spinal cord,where the central pattern generators are located,are interrupted resulting in devastating locomotor impairments and changes in the expression and activation of serotonin and its spinal receptors.The molecular cues that control the precise patterning and targeting of serotonergic inputs onto central pattern generator networks in healthy animals or after injury are still unknown.In our recent research work,we have been particularly interested in Semaphorin7A,which belongs to the Semaphorins family involved in guiding growing axons and controlling plasticity of synaptic connections.In this review,we discuss the role of Semaphorin7A signaling as an important molecular actor that instructs the patterning of serotonin inputs to spinal central pattern generator networks.We show that Semaphorin7A controls the wiring of descending serotonin axons in the spinal cord.Our results reveal that mistargetting of serotonin fibers in the spinal cord is compensated in healthy uninjured Semaphorin7A deficient mice so that their gross locomotion proceeds accurately.We also demonstrate that when the system is challenged with a spinal lesion,the pattern of post-injury serotonin expression is significantly altered in Semaphorin7A deficient mice with specific ectopic targeting of serotonin fibers in the lumbar spinal cord.Compensatory mechanisms in place in uninjured Semaphorin7A deficient mice are lost and injured Semaphorin7A deficient mice exhibit a worsening of their post-injury locomotor abilities.Our findings identify Semaphorin7A as a critical determinant of serotonergic circuit formation in healthy or spinal cord injured mice.

关键词： central pattern generator guidance molecule locomotion recovery rewiring semaphorin7A serotonergic patterning serotonin spinal cord injury

A Rhythmic Motion Control Method Inspired by Board Shoe Racing for a Weight-Bearing Exoskeleton

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Journal of Bionic Engineering 2022年第2期19卷 403-415页

作者： Tianshuo Wang Jie Zhao Dongbao Sui Sikai Zhao Yanhe Zhu State Key Laboratory of Robotics and System Harbin Institute of TechnologyHarbin 150001China

To ensure the flexible walking of the weight-bearing exoskeleton robot,most researchers control the exoskeleton to follow the wearer’s movements and provide force to maintain the current dynamic state.However,due to the limitation of sensing information and computing power,it is difficult for the exoskeleton to provide the wearer reasonable and stable force only based on the dynamic model,especially in switching between swing phase and stance phase.Inspired by China’s traditional sport named board shoe racing,a walking control method based on the cooperation of the human and the exoskeleton is proposed in this paper for a lower-limb exoskeleton named PALExo.Under certain conditions,the exoskeleton itself can walk stably depending on the rhythm signals generated by the central pattern generator(CPG).With certain initiative during walking,it can make proper adjustments according to the human movement.With the help of dynamic simulation software and Genetic Algorithm(GA),the optimized CPG parameters are obtained.Impedance control is introduced to increase the comfort of the wearer.The impedance parameters as well as the CPG parameters are tuned in real time based on feedback.The experiments were conducted with PALExo.The results demonstrate that PALExo can effectively assist the wearer walking with a 45-kg payload benefiting from the proposed method.

关键词： Exoskeleton robot central pattern generator Walking control method

Analysis and Design of Asymmetric Oscillation for Caterpillar-Like Locomotion

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Journal of Bionic Engineering 2015年第2期12卷 190-203页

作者： Guoyuan Li Wei Li Jianwei Zhang Houxiang Zhang Faculty of Maritime Technology and Operations Aalesund University College Aalesund 6009 Norway Department of Computer Science University of Hamburg Hamburg 22527 Germany

Caterpillar crawling is distinct from that of other limbless animals. It is simple but efficient. This paper presents a novel mechanism to duplicate the movement to a modular caterpillar-like robot. First, how caterpillars move in nature is investigated and analyzed systematically. Two key locomotive properties are abstracted from the body shape of caterpillars during crawling. Then, based on a morphological mapping, a hypothesis of asymmetric oscillation with a ratio of two is proposed, followed by a thorough analysis of the kinematics of the caterpillar-like robot. The asymmetric oscillating mechanism is proved capable of generating stable caterpillar-like locomotion. Next, taking advantage of the two locomotive properties and the hypothesis, a new central pattern generator （CPG） model is designed as the controller of the robot. The model can not only generate the signal as expected, but also provide explicit control parameters for online modulation. Finally, simulation and on-site experiments are carried out. The results confirm that the proposed method is effective for caterpillar-like locomotion.

关键词： asymmetric oscillation kinematic analysis central pattern generator caterpillar-like locomotion

An Approach for Adaptive Limbless Locomotion Using a CPG-Based Reflex Mechanism

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Journal of Bionic Engineering 2014年第3期11卷 389-399页

作者： Guoyuan Li Houxiang Zhang Jianwei Zhang Hans Petter Hildre Faculty of Maritime Technology and Operations Aalesund University College Aalesund 6009 Norway Department of Computer Science University of Hamburg Hamburg 22527 Germany

Animals＇ free movement in natural environments has attracted many researchers to explore control methods for bio-inspired robots. This paper presents a novel reflex mechanism based on a central pattern generator （CPG） for adaptive locomotion of limbless robots. First, inspired by the concept of reflex arc, the reflex mechanism is designed on a connectionist CPG model. Since the CPG model inspired by the spinal cord of lampreys is developed at the neuron level, it provides a possible natural solution for sensory reflex integration. Therefore, sensory neurons that bridge the external stimuli and the CPG model, together with the concept of reflex arc, are utilized for designing the sensory reflex mechanism. Then, a border reflex and a body reflex are further developed and applied on the ends and the middle part of a limbless robot, respectively. Finally, a ball hitting scenario and a corridor passing scenario are designed to verify the proposed method. Results of simulations and on-site experiments show the feasibility and effectiveness of the reflex mechanism in realizing fast response and adaptive limbless locomotion.

关键词： sensory reflex mechanism reflex arc central pattern generator limbless locomotion

Stable Transition of Quadruped Rhythmic Motion Using the Tracking Differentiator

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Journal of Harbin Institute of Technology(New Series) 2015年第5期22卷 9-16页

作者： Xiaoqi Li Wei Wang Jianqiang Yi Institute of Automation Chinese Academy of Sciences

Since the quadruped robot possesses predominant environmental adaptability,it is expected to be employed in nature environments. In some situations,such as ice surface and tight space,the quadruped robot is required to lower the height of center of gravity( COG) to enhance the stability and maneuverability. To properly handle these situations,a quadruped controller based on the central pattern generator( CPG) model,the discrete tracking differentiator( TD) and proportional-derivative( PD) sub-controllers is presented. The CPG is used to generate basic rhythmic motion for the quadruped robot. The discrete TD is not only creatively employed to implement the transition between two different rhythmic medium values of the CPG which results in the adjustment of the height of COG of the quadruped robot,but also modified to control the transition duration which enables the quadruped robot to achieve the stable transition. Additionally,two specific PD sub-controllers are constructed to adjust the oscillation amplitude of the CPG,so as to avoid the severe deviation in the transverse direction during transition locomotion. Finally,the controller is validated on a quadruped model. A tunnel with variable height is built for the quadruped model to travel through. The simulation demonstrates the severe deviation without the PD sub-controllers,and the reduced deviation with the PD sub-controllers.

关键词： quadruped robot center of gravity central pattern generator discrete tracking differentiator proportional-derivative sub-controller

Design and Analysis of Gecko-like Robot

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Chinese Journal of Mechanical Engineering 2011年第2期24卷 224-236页

作者： MENG Cai WANG Tianmiao GUAN Shengguo ZHANG Long WANG Jing LI Xiaohu School of Astronautics Beihang University Beijing 100191 China School of Mechanical Engineering andAutomation Reihang University Beijing 100191 China School of Mechanical Engineering Beijing University of Science and Technology Beijing 100083 China

Gecko-like robot（Geckobot）,an important branch of bionic robotics,is a robot that simulates gecko＇s capacity to climb walls and ceilings.The work environment of the traditional wall-climbing robot is greatly limited as the moving structure and adsorption principle of the robot have nothing to do with the real gecko.However,the adsorption principle and moving mode of the real gecko can provide a new way to break through the restrictions of the traditional wall-climbing robot.Inspired by the moving mechanism of geckos, this paper develops the Geckobot with motile body.Two types of Geckobots are addressed：one with compliant flat bar as the body,and the other with prismatic joint as the body.The compliant body not only resembles the moving mode of the real gecko body,but also simplifies the Geckobot＇s structure.The prismatic joint body is used to adapt the change of body length in ground-to-wall transition. The gait planning on the plane and the transition between perpendicular intersectional planes is discussed,with an emphasis on the analysis of the kinematics degree of freedom（DOF） and body posture.central pattern generator（CPG） neural network is realized in LabVIEW and utilized to control Geckobot＇s movement.The CPG scheme in Lab VIEW is given,and how CPG is used to control Geckobot to turn or move forward is explored.Simulations are conducted in ADAMS to verify the feasibility of the structure design and gait planning and to acquire some parameters for practical Geckobot development.The experiment with Geckobot-Ⅰand Geckobot-Ⅱon their crawling capacity on the plane and the ground-to-wall transition finds that the robot can complete the crawling movement and ground-to-wall transition,verifying the feasibility of the structure design,gait planning and the CPG motion control.The Geckobot structure design approach,gait planning and the CPG motion control presented would be useful for the research on wall-climbing robots.

关键词： gecko-like robot structure design gait planning ground-to-wall transition central pattern generator

Intraspinal microstimulation A novel technique for the functional recovery of spinal cord injury

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Neural Regeneration Research 2010年第16期5卷 1249-1255页

作者： Hua Zhang Liqun Feng Yuping Wang Department of Neurology Xuanwu Hospital Capital Medical University Beijing 100053 China Department of Neurology Anzhen Hospital Capital Medical University Beijing 100029 China

Nonspecific neuronal activity elicited by intraspinal microstimulation in the intermediate and ventral gray matter of thoracic spinal segments caudal to a complete spinal cord transection significantly increased the rat hindlimb Basso, Beattie, Bresnahan locomotor score by activating the central pattem generator located in the lumbar spinal cord. However, the best region for intraspinal microstimulation is unclear. Using an incomplete spinal cord injury model at T8, we compared the use of intraspinal microstimulation to activate the spinal cord in rats with a spontaneous recovery group. The intraspinal microstimulation group recovered sooner and showed three kinds of movement： the left hindlimb, the left hindlimb toes, and the paraspinal muscles and tails. These had different microstimulation thresholds. There was mild hyperplasia of the astrocytes surrounding the tips of the microelectrodes and slight inflammatory reactions nearby. These results indicate that implantation of microelectrodes was relatively safe and induced minimal damage to the lumbar-sacral spinal cord. Intraspinal microstimulation in the lumbar sacral spinal cord may improve leg movements after spinal cord injury. Non-specific intraspinal microstimulation may be a novel technique for the recovery of spinal cord injuries.

关键词： intraspinal microstimulation spinal cord injury central pattern generator propriospinal neurons neural regeneration