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 Genetic study of motor functions in Drosophila melanogaster

2012 ◽  
Vol 10 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Sergey A Fedotov ◽  
Julia V Bragina ◽  
Nataliya G Besedina ◽  
Larisa V Danilenkova ◽  
Elena A Kamysheva ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Motor Activity ◽  
Genomic Dna ◽  
Molecular Mechanisms ◽  
Central Pattern Generators ◽  
Courtship Song ◽  
P Element ◽  
Rhythmic Motor ◽  
Pattern Generators ◽  
First Time

To investigate molecular mechanisms of central pattern generators (CPG s) functioning, we carried out a screening of collection of Drosophila P-insertional mutants for strong deviations in locomotion and courtship song. In 21 mutants, the site of the P-insertion was localized by sequencing of the fragments of genomic DNA flanking the P-element. Bioinformational analysis revealed a list of candidate genes, potential players in development and functioning of CPG s. Possible involvement of certain identified genes in rhythmic motor activity is suggested for the first time (CG15630, Map205).

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 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.

scholarly journals The Role of Supraspinal Structures for Recovery after SCI: From Motor Dysfunction to Mental Health

2021 ◽  
Author(s):  
Braniff de la Torre-Valdovinos ◽  
Laura Paulina Osuna-Carrasco ◽  
Carlos Cuellar
Keyword(s):  
Mental Health ◽  
Spinal Cord ◽  
Electrical Stimulation ◽  
Central Pattern Generators ◽  
Clinical Manifestations ◽  
Motor Dysfunction ◽  
Cell Therapies ◽  
Cord Injury ◽  
Robotic Devices ◽  
Pattern Generators

Neural circuitry controlling limbed locomotion is located in the spinal cord, known as Central Pattern Generators (CPGs). After a traumatic Spinal Cord Injury (SCI), ascending and descending tracts are damaged, interrupting the communication between CPGs and supraspinal structures that are fundamental to initiate, control and adapt movement to the environment. Although low vertebrates and some mammals regain some physiological functions after a spinal insult, the capacity to recover in hominids is rather limited. The consequences after SCI include physiological (sensory, autonomic and motor) and mental dysfunctions, which causes a profound impact in social and economic aspects of patients and their relatives Despite the recent progress in the development of therapeutic strategies for SCI, there is no satisfactory agreement for choosing the best treatment that restores the affected functions of people suffering the devastating consequences after SCI. Studies have described that patients with chronic SCI can achieve some degree of neurorestoration with strategies that include physical rehabilitation, neuroprosthesis, electrical stimulation or cell therapies. Particularly in the human, the contribution of supraspinal structures to the clinical manifestations of gait deficits in people with SCI and its potential role as therapeutic targets is not well known. Additionally, mental health is considered fundamental as it represents the first step to overcome daily adversities and to face progression of this unfortunate condition. This chapter focuses on the consequences of spinal cord disconnection from supraspinal structures, from motor dysfunction to mental health. Recent advancements on the study of supraspinal structures and combination of different approaches to promote recovery after SCI are discussed. Promising strategies are used alone or in combination and include drugs, physical exercise, robotic devices, and electrical stimulation.

Plastic Changes After Spinal Cord Injury

2019 ◽  
Author(s):  
Kaitlin Farrell ◽  
Megan R. Detloff ◽  
John D. Houle
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Central Pattern Generators ◽  
Sensory Stimulation ◽  
Cellular Tissue ◽  
Primary Response ◽  
Sensory Loss ◽  
Cord Injury ◽  
Plastic Changes ◽  
Pattern Generators

Spinal cord injury has instantaneous, destructive effects on bodily functions, as readily demonstrated by muscle paralysis and non-responsiveness to sensory stimulation. This primary response has underlying features at molecular, cellular, tissue and organ levels which will, in a relatively brief time, initiate a secondary cascade of events that exacerbates the extent of the primary focus of damage. Interestingly, the initial extent of motor and sensory loss often is followed by limited, but significant spontaneous functional recovery. Recovery may be due to intrinsic central pattern generators such as for locomotion, the uncovering of dormant anatomical and physiological pathways such as the crossed phrenic for respiration, or to the sprouting of undamaged axons within the spinal cord to establish new connections around or across the injury site. Together the responses to injury and spontaneous efforts for repair represent plastic changes in the central nervous system (CNS) that may result in meaningful functional outcomes, though aberrant sprouting is a possible negative consequence of neuroplasticity that lends caution to the desire for extensive but uncontrolled sprouting.

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

1994 ◽  
Vol 71 (6) ◽  
pp. 1-1
Author(s):  
A. D. McClellan ◽  
W. Jang
Keyword(s):  
Spinal Cord ◽  
Phase Shift ◽  
Computer Modeling ◽  
Computer Simulations ◽  
Central Pattern Generators ◽  
Phase Delay ◽  
Phase Vector ◽  
Synaptic Inputs ◽  
Pattern Generators ◽  
Oscillator Phase

Pages 2442–2454: A. D. McClellan and W. Jang, “Mechanosensory inputs to the central pattern generators for locomotion in the lamprey spinal cord: resetting, entrainment, and computer modeling.” The oscillator PRCs (Fig. 2 B) used in the computer simulations (Figs. 10—14) were inverted which was implemented by making the PRC scalars negative See PDF for Equation Thus synaptic inputs to an oscillator that produce phase delay (phase advance), which is represented by positive (negative) values in the PRCs in Fig. 2 B, will contribute a negative (positive) phase shift to the expression for oscillator phase ( Eq. 1) so that it takes a longer (shorter) time for the oscillator phase vector to complete one cycle.

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