Caenorhabditis elegans
            excitatory ventral cord motor neurons derive rhythm for body undulation

The intrinsic oscillatory activity of central pattern generators underlies motor rhythm. We review and discuss recent findings that address the origin of Caenorhabditis elegans motor rhythm. These studies propose that the A- and mid-body B-class excitatory motor neurons at the ventral cord function as non-bursting intrinsic oscillators to underlie body undulation during reversal and forward movements, respectively. Proprioception entrains their intrinsic activities, allows phase-coupling between members of the same class motor neurons, and thereby facilitates directional propagation of undulations. Distinct pools of premotor interneurons project along the ventral nerve cord to innervate all members of the A- and B-class motor neurons, modulating their oscillations, as well as promoting their bi-directional coupling. The two motor sub-circuits, which consist of oscillators and descending inputs with distinct properties, form the structural base of dynamic rhythmicity and flexible partition of the forward and backward motor states. These results contribute to a continuous effort to establish a mechanistic and dynamic model of the C. elegans sensorimotor system. C. elegans exhibits rich sensorimotor functions despite a small neuron number. These findings implicate a circuit-level functional compression. By integrating the role of rhythm generation and proprioception into motor neurons, and the role of descending regulation of oscillators into premotor interneurons, this numerically simple nervous system can achieve a circuit infrastructure analogous to that of anatomically complex systems. C. elegans has manifested itself as a compact model to search for general principles of sensorimotor behaviours. This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling C. elegans at cellular resolution’.

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Excitatory Motor Neurons are Local Central Pattern Generators in an Anatomically Compressed Motor Circuit for Reverse Locomotion

10.1101/135418 ◽

2017 ◽

Cited By ~ 2

Author(s):

Shangbang Gao ◽

Sihui Asuka Guan ◽

Anthony D. Fouad ◽

Jun Meng ◽

Taizo Kawano ◽

...

Keyword(s):

Motor Neurons ◽

Calcium Imaging ◽

Central Pattern Generators ◽

Oscillatory Activity ◽

Intrinsic Activity ◽

C Elegans ◽

Class A ◽

Cell Ablation ◽

Pattern Generators

AbstractCentral pattern generators are cell‐ or network-driven oscillators that underlie motor rhythmicity. The existence and identity of C. elegans CPGs remain unknown. Through cell ablation, electrophysiology, and calcium imaging, we identified oscillators for reverse locomotion. We show that the cholinergic and excitatory class A motor neurons exhibit intrinsic and oscillatory activity, and such an activity can drive reverse locomotion without premotor interneurons. Regulation of their oscillatory activity, either through effecting an endogenous constituent of oscillation, the P/Q/N high voltage-activated calcium channel UNC-2, or, via dual regulation – inhibition and activation ‐ by the descending premotor interneurons AVA, determines the propensity, velocity, and sustention of reverse locomotion. Thus, the reversal motor executors themselves serve as oscillators; regulation of their intrinsic activity controls the reversal motor state. These findings exemplify anatomic and functional compression: motor executors integrate the role of rhythm generation in a locomotor network that is constrained by small cell numbers.

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Functionally asymmetric motor neurons coordinate locomotion of Caenorhabditis elegans

10.1101/244434 ◽

2018 ◽

Cited By ~ 1

Author(s):

Oleg Tolstenkov ◽

Petrus Van der Auwera ◽

Jana F. Liewald ◽

Wagner Steuer Costa ◽

Olga Bazhanova ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Gap Junctions ◽

Motor Neurons ◽

Nerve Cord ◽

Ventral Nerve Cord ◽

Body Wave ◽

Central Pattern Generators ◽

Physiological Data ◽

C Elegans ◽

Pattern Generators

SummaryInvertebrate nervous systems are valuable models for fundamental principles of the control of behavior. Ventral nerve cord (VNC) motor neurons in Caenorhabditis elegans represent one of the best studied locomotor circuits, with known connectivity and functional information about most of the involved neuron classes. However, for one of those, the AS motor neurons (AS MNs), no physiological data is available. Combining specific expression and selective illumination, we precisely targeted AS MNs by optogenetics and addressed their role in the locomotion circuit. After photostimulation, AS MNs induce currents in post-synaptic body wall muscles (BWMs), exhibiting an initial asymmetry of excitatory output. This may facilitate complex regulatory motifs for adjusting direction during navigation. By behavioral and photo-inhibition experiments, we show that AS MNs contribute to propagation of the antero-posterior body wave during locomotion. By Ca2+-imaging in AS MNs and in their synaptic partners, we also reveal that AS MNs play a role in mediating forward and backward locomotion by integrating activity of premotor interneurons (PINs), as well as in coordination of the dorso-ventral body wave. AS MNs do not exhibit pacemaker properties, but potentially gate VNC central pattern generators (CPGs), as indicated by ceasing of locomotion when AS MNs are hyperpolarized. AS MNs provide positive feedback to the PIN AVA via gap junctions, a feature found also in other locomotion circuits. In sum, AS MNs have essential roles in coordinating locomotion, combining several functions, and emphasizing the compressed nature of the C. elegans nervous system in comparison to higher animals.HighlightsA class of motor neurons with unidentified function – AS cholinergic motor neurons - was characterized in C. elegans.AS neurons show asymmetry in both input and output and are specialized in coordination of dorso-ventral undulation bends.AS neurons mediate antero-posterior propagation of the undulatory body wave during locomotion.AS neurons integrate signals for forward and reverse locomotion from premotor interneurons and may gate ventral nerve cord central pattern generators (CPGs) via gap junctions.

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A descending pathway facilitates undulatory wave propagation in Caenorhabditis elegans through gap junctions

10.1101/131490 ◽

2017 ◽

Author(s):

Tianqi Xu ◽

Jing Huo ◽

Shuai Shao ◽

Michelle Po ◽

Taizo Kawano ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Gap Junctions ◽

Motor Neuron ◽

Motor Neurons ◽

Central Pattern Generators ◽

The Body ◽

C Elegans ◽

Bending Waves ◽

Forward Locomotion ◽

Type Motor

Descending signals from the brain play critical roles in controlling and modulating locomotion kinematics. In the Caenorhabditis elegans nervous system, descending AVB premotor interneurons exclusively form gap junctions with B-type motor neurons that drive forward locomotion. We combined genetic analysis, optogenetic manipulation, and computational modeling to elucidate the function of AVB-B gap junctions during forward locomotion. First, we found that some B-type motor neurons generated intrinsic rhythmic activity, constituting distributed central pattern generators. Second, AVB premotor interneurons drove bifurcation of B-type motor neuron dynamics, triggering their transition from stationary to oscillatory activity. Third, proprioceptive couplings between neighboring B-type motor neurons entrained the frequency of body oscillators, forcing coherent propagation of bending waves. Despite substantial anatomical differences between the worm motor circuit and those in higher model organisms, we uncovered converging principles that govern coordinated locomotion.Significance StatementA deep understanding of the neural basis of motor behavior must integrate neuromuscular dynamics, mechanosensory feedback, as well as global command signals, to predict behavioral dynamics. Here, we report on an integrative approach to defining the circuit logic underlying coordinated locomotion in C. elegans. Our combined experimental and computational analysis revealed that (1) motor neurons in C. elegans could function as intrinsic oscillators; (2) Descending inputs and proprioceptive couplings work synergistically to facilitate the sequential activation of motor neuron activities, allowing bending waves to propagate efficiently along the body. Our work thus represents a key step towards an integrative view of animal locomotion.

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The conserved ASCL1/MASH-1 ortholog HLH-3 specifies sex-specific ventral cord motor neuron fate in C. elegans

10.1101/2020.06.04.134767 ◽

2020 ◽

Author(s):

Lillian M. Perez ◽

Aixa Alfonso

Keyword(s):

Motor Neuron ◽

Cell Fate ◽

Motor Neurons ◽

Bhlh Protein ◽

Differentiation Markers ◽

C Elegans ◽

Ventral Cord ◽

Neural Specification

ABSTRACTNeural specification can be regulated by one or many transcription factors. Here we identify a novel role for one conserved proneural factor, the bHLH protein HLH-3, implicated in the specification of sex-specific ventral cord motor neurons in C. elegans. In the process of characterizing the role of hlh-3 in neural specification, we document that differentiation of the ventral cord type C neurons, VCs, within their motor neuron class, is dynamic in time and space. Expression of VC class-specific and subclass-specific identity genes is distinct through development and dependent on where they are along the A-P axis (and their position in proximity to the vulva). Our characterization of the expression of VC class and VC subclass-specific differentiation markers in the absence of hlh-3 function reveals that VC fate specification, differentiation, and morphology requires hlh-3 function. Finally, we conclude that hlh-3 cell-autonomously specifies VC cell fate.

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Potential role of a ventral nerve cord central pattern generator in forward and backward locomotion in Caenorhabditis elegans

Network Neuroscience ◽

10.1162/netn_a_00036 ◽

2018 ◽

Vol 2 (3) ◽

pp. 323-343 ◽

Cited By ~ 10

Author(s):

Erick O. Olivares ◽

Eduardo J. Izquierdo ◽

Randall D. Beer

Keyword(s):

Nerve Cord ◽

Ventral Nerve Cord ◽

Computational Models ◽

Neural Circuit ◽

Central Pattern Generators ◽

C Elegans ◽

Segmentation Analysis ◽

Pattern Generators ◽

Neural Unit

C. elegans locomotes in an undulatory fashion, generating thrust by propagating dorsoventral bends along its body. Although central pattern generators (CPGs) are typically involved in animal locomotion, their presence in C. elegans has been questioned, mainly because there has been no evident circuit that supports intrinsic network oscillations. With a fully reconstructed connectome, the question of whether it is possible to have a CPG in the ventral nerve cord (VNC) of C. elegans can be answered through computational models. We modeled a repeating neural unit based on segmentation analysis of the connectome. We then used an evolutionary algorithm to determine the unknown physiological parameters of each neuron so as to match the features of the neural traces of the worm during forward and backward locomotion. We performed 1,000 evolutionary runs and consistently found configurations of the neural circuit that produced oscillations matching the main characteristic observed in experimental recordings. In addition to providing an existence proof for the possibility of a CPG in the VNC, we suggest a series of testable hypotheses about its operation. More generally, we show the feasibility and fruitfulness of a methodology to study behavior based on a connectome, in the absence of complete neurophysiological details.

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The Functional Connectivity between the Locust Leg Pattern Generating Networks and the Subesophageal Ganglion Higher Motor Center

10.1101/226167 ◽

2017 ◽

Cited By ~ 2

Author(s):

Daniel Knebel ◽

Jan Rillich ◽

Leonard Nadler ◽

Hans-Joachim Pflueger ◽

Amir Ayali

Keyword(s):

Motor Neurons ◽

Central Pattern Generators ◽

Subesophageal Ganglion ◽

Motor Center ◽

Coupling Pattern ◽

Descending Interneurons ◽

Pattern Generators ◽

Leg Movements

AbstractInteractions among different neuronal circuits are essential for adaptable coordinated behavior. Specifically, higher motor centers and central pattern generators (CPGs) induce rhythmic leg movements that act in concert in the control of locomotion. Here we explored the relations between the subesophageal ganglion (SEG) and thoracic leg CPGs in the desert locust. Backfill staining revealed about 300 SEG descending interneurons (DINs) and some overlap with the arborization of DINs and leg motor neurons. In accordance, in in-vitro preparations, electrical stimulation applied to the SEG excited these neurons, and in some cases also induced CPGs activity. Additionally, we found that the SEG regulates the coupling pattern among the CPGs: when the CPGs were activated pharmacologically, inputs from the SEG were able to synchronize contralateral CPGs. This motor output was correlated to the firing of SEG descending and local interneurons. Altogether, these findings point to a role of the SEG in both activating leg CPGs and in coordinating their oscillations, and suggest parallels between the SEG and the brainstem of vertebrates.

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Descending pathway facilitates undulatory wave propagation in Caenorhabditis elegans through gap junctions

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1717022115 ◽

2018 ◽

Vol 115 (19) ◽

pp. E4493-E4502 ◽

Cited By ~ 24

Author(s):

Tianqi Xu ◽

Jing Huo ◽

Shuai Shao ◽

Michelle Po ◽

Taizo Kawano ◽

...

Keyword(s):

Wave Propagation ◽

Caenorhabditis Elegans ◽

Gap Junctions ◽

Motor Neurons ◽

Rhythmic Activity ◽

Oscillatory Activity ◽

Model Organisms ◽

C Elegans ◽

Forward Locomotion ◽

Type Motor

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Characterization of Caenorhabditis elegans Homologs of the Down Syndrome Candidate Gene DYRK1A

Genetics ◽

10.1093/genetics/163.2.571 ◽

2003 ◽

Vol 163 (2) ◽

pp. 571-580 ◽

Cited By ~ 1

Author(s):

William B Raich ◽

Celine Moorman ◽

Clay O Lacefield ◽

Jonah Lehrer ◽

Dusan Bartsch ◽

...

Keyword(s):

Down Syndrome ◽

Caenorhabditis Elegans ◽

Trisomy 21 ◽

Gene Dosage ◽

Inducible Promoters ◽

C Elegans ◽

Dual Specificity ◽

Specificity Protein

Abstract The pathology of trisomy 21/Down syndrome includes cognitive and memory deficits. Increased expression of the dual-specificity protein kinase DYRK1A kinase (DYRK1A) appears to play a significant role in the neuropathology of Down syndrome. To shed light on the cellular role of DYRK1A and related genes we identified three DYRK/minibrain-like genes in the genome sequence of Caenorhabditis elegans, termed mbk-1, mbk-2, and hpk-1. We found these genes to be widely expressed and to localize to distinct subcellular compartments. We isolated deletion alleles in all three genes and show that loss of mbk-1, the gene most closely related to DYRK1A, causes no obvious defects, while another gene, mbk-2, is essential for viability. The overexpression of DYRK1A in Down syndrome led us to examine the effects of overexpression of its C. elegans ortholog mbk-1. We found that animals containing additional copies of the mbk-1 gene display behavioral defects in chemotaxis toward volatile chemoattractants and that the extent of these defects correlates with mbk-1 gene dosage. Using tissue-specific and inducible promoters, we show that additional copies of mbk-1 can impair olfaction cell-autonomously in mature, fully differentiated neurons and that this impairment is reversible. Our results suggest that increased gene dosage of human DYRK1A in trisomy 21 may disrupt the function of fully differentiated neurons and that this disruption is reversible.

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The Caenorhabditis elegans odr-2 Gene Encodes a Novel Ly-6-Related Protein Required for Olfaction

Genetics ◽

10.1093/genetics/157.1.211 ◽

2001 ◽

Vol 157 (1) ◽

pp. 211-224 ◽

Cited By ~ 1

Author(s):

Joseph H Chou ◽

Cornelia I Bargmann ◽

Piali Sengupta

Keyword(s):

Caenorhabditis Elegans ◽

Motor Neurons ◽

Amino Terminus ◽

Signaling Proteins ◽

Related Protein ◽

Olfactory Neurons ◽

Unique Role ◽

C Elegans ◽

Founding Member ◽

High Concentrations

Abstract Caenorhabditis elegans odr-2 mutants are defective in the ability to chemotax to odorants that are recognized by the two AWC olfactory neurons. Like many other olfactory mutants, they retain responses to high concentrations of AWC-sensed odors; we show here that these residual responses are caused by the ability of other olfactory neurons (the AWA neurons) to be recruited at high odor concentrations. odr-2 encodes a membrane-associated protein related to the Ly-6 superfamily of GPI-linked signaling proteins and is the founding member of a C. elegans gene family with at least seven other members. Alternative splicing of odr-2 yields three predicted proteins that differ only at the extreme amino terminus. The three isoforms have different promoters, and one isoform may have a unique role in olfaction. An epitope-tagged ODR-2 protein is expressed at high levels in sensory neurons, motor neurons, and interneurons and is enriched in axons. The AWC neurons are superficially normal in their development and structure in odr-2 mutants, but their function is impaired. Our results suggest that ODR-2 may regulate AWC signaling within the neuronal network required for chemotaxis.

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Mutations Affecting Nerve Attachment of Caenorhabditis elegans

Genetics ◽

10.1093/genetics/157.4.1611 ◽

2001 ◽

Vol 157 (4) ◽

pp. 1611-1622 ◽

Cited By ~ 1

Author(s):

Go Shioi ◽

Michinari Shoji ◽

Masashi Nakamura ◽

Takeshi Ishihara ◽

Isao Katsura ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Nerve Cord ◽

Ventral Nerve Cord ◽

Body Wall ◽

The Body ◽

Genetic Loci ◽

Muscle Attachment ◽

C Elegans ◽

Ventral Cord ◽

Excretory Canal

Abstract Using a pan-neuronal GFP marker, a morphological screen was performed to detect Caenorhabditis elegans larval lethal mutants with severely disorganized major nerve cords. We recovered and characterized 21 mutants that displayed displacement or detachment of the ventral nerve cord from the body wall (Ven: ventral cord abnormal). Six mutations defined three novel genetic loci: ven-1, ven-2, and ven-3. Fifteen mutations proved to be alleles of previously identified muscle attachment/positioning genes, mup-4, mua-1, mua-5, and mua-6. All the mutants also displayed muscle attachment/positioning defects characteristic of mua/mup mutants. The pan-neuronal GFP marker also revealed that mutants of other mua/mup loci, such as mup-1, mup-2, and mua-2, exhibited the Ven defect. The hypodermis, the excretory canal, and the gonad were morphologically abnormal in some of the mutants. The pleiotropic nature of the defects indicates that ven and mua/mup genes are required generally for the maintenance of attachment of tissues to the body wall in C. elegans.

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