Distributed Rhythm Generators Underlie Caenorhabditis elegans Forward Locomotion

ABSTRACTCoordinated rhythmic movements are ubiquitous in animal behavior. In many organisms, chains of neural oscillators underlie the generation of these rhythms. In C. elegans, locomotor wave generation has been poorly understood; in particular, it is unclear where in the circuit rhythms are generated, and whether there exists more than one such generator. We used optogenetic and ablation experiments to probe the nature of rhythm generation in the locomotor circuit. We found that multiple sections of forward locomotor circuitry are capable of independently generating rhythms. By perturbing different components of the motor circuit, we localize the source of secondary rhythms to cholinergic motor neurons in the midbody. Using rhythmic optogenetic perturbation we demonstrate bidirectional entrainment of oscillations between different body regions. These results show that, as in many other vertebrates and invertebrates, the C. elegans motor circuit contains multiple oscillators that coordinate activity to generate behavior.

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Distributed rhythm generators underlie Caenorhabditis elegans forward locomotion

eLife ◽

10.7554/elife.29913 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 24

Author(s):

Anthony D Fouad ◽

Shelly Teng ◽

Julian R Mark ◽

Alice Liu ◽

Pilar Alvarez-Illera ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Motor Neurons ◽

Animal Behavior ◽

Rhythm Generation ◽

Rhythmic Movements ◽

Neural Oscillators ◽

Motor Circuit ◽

C Elegans ◽

Body Regions ◽

Forward Locomotion

Coordinated rhythmic movements are ubiquitous in animal behavior. In many organisms, chains of neural oscillators underlie the generation of these rhythms. In C. elegans, locomotor wave generation has been poorly understood; in particular, it is unclear where in the circuit rhythms are generated, and whether there exists more than one such generator. We used optogenetic and ablation experiments to probe the nature of rhythm generation in the locomotor circuit. We found that multiple sections of forward locomotor circuitry are capable of independently generating rhythms. By perturbing different components of the motor circuit, we localize the source of secondary rhythms to cholinergic motor neurons in the midbody. Using rhythmic optogenetic perturbation, we demonstrate bidirectional entrainment of oscillations between different body regions. These results show that, as in many other vertebrates and invertebrates, the C. elegans motor circuit contains multiple oscillators that coordinate activity to generate behavior.

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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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Persistent thermal input controls steering behavior in Caenorhabditis elegans

10.1101/2020.04.29.067876 ◽

2020 ◽

Author(s):

Muneki Ikeda ◽

Hirotaka Matsumoto ◽

Eduardo J. Izquierdo

Keyword(s):

Caenorhabditis Elegans ◽

Motor Neurons ◽

Subtle Difference ◽

Environmental Signals ◽

C Elegans ◽

Neural Activities ◽

Free Living Nematode ◽

Forward Locomotion ◽

Higher Temperature ◽

Spectrum Decomposition

AbstractMotile organisms actively detect environmental signals and migrate to a preferable environment. Especially, small-size animals convert subtle difference in sensory input into orientation behavioral output for directly steering toward a destination, but the neural mechanisms underlying steering behavior remain elusive. Here, we analyze a C. elegans thermotactic behavior in which a small number of neurons are shown to mediate steering toward a destination temperature. We construct a neuroanatomical model and use an evolutionary algorithm to find configurations of the model that reproduce empirical thermotactic behavior. We find that, in all the evolved models, steering rates are modulated by persistent thermal signals sensed through forward locomotion. Persistent temperature increment lessens steering rates resulting in straight movement of model worms, whereas temperature decrement enlarges steering rates resulting in curvy movement. This relationship between temperature change and steering rates reproduces the empirical thermotactic migration up thermal gradients and steering bias toward higher temperature. Further, spectrum decomposition of neural activities in model worms show that thermal signals are transmitted from a sensory neuron to motor neurons on the longer time scale than sinusoidal locomotion of C. elegans. Our results suggest that employments of persistent sensory signals enable small-size animals to steer toward a destination in natural environment with variable, noisy, and subtle cues.Author summaryA free-living nematode Caenorhabditis elegans memorizes an environmental temperature and steers toward the remembered temperature on a thermal gradient. How does the C. elegans brain, consisting of 302 neurons, achieve this thermotactic steering behavior? Here, we address this question through neuroanatomical modeling and simulation analyses. We find that persistent thermal input modulates steering rates of model worms; worms run straight when they move up to a destination temperature, whereas run crookedly when move away from the destination. As a result, worms steer toward the destination temperature as observed in experiments. Our analysis also shows that persistent thermal signals are transmitted from a thermosensory neuron to dorsal and ventral neck motor neurons, regulating the balance of dorsoventral muscle contractions of model worms and generating steering behavior. This study indicates that C. elegans can steer toward a destination temperature without processing acute thermal input that informs to which direction it should steer. Such indirect mechanism of steering behavior is potentially employed in other motile organisms.

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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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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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Identification Of A Novel Gene Altered In The RQ1 Mutant Strain Affecting Motor Axon Migration In Caenorhabditis Elegans

10.32920/ryerson.14662620 ◽

2021 ◽

Author(s):

Haider Z. Naqvi

Keyword(s):

Caenorhabditis Elegans ◽

Axon Guidance ◽

Motor Neurons ◽

Genetic Background ◽

Germ Line ◽

Strong Indication ◽

Wild Type ◽

C Elegans ◽

Novel Gene ◽

Mutation Region

Novel genetic enhancer screens were conducted targeting mutants involved in the guidance of axons of the DA and DB classes of motor neurons in C. elegans. These mutations are expected in genes that function in parallel to the unc-g/Netrin pathway. The screen was conducted in an unc-5(e53) genetic background and enhancers of the axon guidance defects caused by the absence of UNC-5 were identified. Three mutants were previously identified in the screen called rq1, rq2 and rq3 and two additional mutants called H2-4 and M1-3, were isolated in this study. In order to identify the gene affected by the rq1 mutation, wild-type copies of genes in the mapped rq1 mutation region were injected into the mutants to rescue the phenotypic defects. This is a strong indication that the gene of interest is a novel gene called H04D03.1. Promising results indicate that the H04D03.1 protein also works in germ-line apoptosis.

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Functional Genetic Screen to Identify Interneurons Governing Behaviorally Distinct Aspects of Drosophila Larval Motor Programs

10.1101/041061 ◽

2016 ◽

Cited By ~ 1

Author(s):

Matt Q. Clark ◽

Stephanie J. McCumsey ◽

Sereno Lopez-Darwin ◽

Ellie S. Heckscher ◽

Chris Q. Doe

Keyword(s):

Motor Neurons ◽

Animal Behavior ◽

Motor Program ◽

Genetic Screen ◽

Muscle Contractions ◽

Specific Expression ◽

Motor Programs ◽

Secondary Screen ◽

Forward Locomotion ◽

Sparse Pattern

AbstractDrosophila larval crawling is an attractive system to study patterned motor output at the level of animal behavior. Larval crawling consists of waves of muscle contractions generating forward or reverse locomotion. In addition, larvae undergo additional behaviors including head casts, turning, and feeding. It is likely that some neurons are used in all these behaviors (e.g. motor neurons), but the identity (or even existence) of neurons dedicated to specific aspects of behavior is unclear. To identify neurons that regulate specific aspects of larval locomotion, we performed a genetic screen to identify neurons that, when activated, could elicit distinct motor programs. We used 165 Janelia CRM-Gal4 lines – chosen for sparse neuronal expression – to express the warmth-inducible neuronal activator TrpA1 and screened for locomotor defects. The primary screen measured forward locomotion velocity, and we identified 63 lines that had locomotion velocities significantly slower than controls following TrpA1 activation (28°C). A secondary screen was performed on these lines, revealing multiple discrete behavioral phenotypes including slow forward locomotion, excessive reverse locomotion, excessive turning, excessive feeding, immobile, rigid paralysis, and delayed paralysis. While many of the Gal4 lines had motor, sensory, or muscle expression that may account for some or all of the phenotype, some lines showed specific expression in a sparse pattern of interneurons. Our results show that distinct motor programs utilize distinct subsets of interneurons, and provide an entry point for characterizing interneurons governing different elements of the larval motor program.

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A Dynamic Body Model of the NematodeC. eleganswith Neural Oscillators

Journal of Robotics and Mechatronics ◽

10.20965/jrm.2005.p0318 ◽

2005 ◽

Vol 17 (3) ◽

pp. 318-326 ◽

Cited By ~ 10

Author(s):

Michiyo Suzuki ◽

◽

Takeshi Goto ◽

Toshio Tsuji ◽

Hisao Ohtake ◽

...

Keyword(s):

Computer Simulation ◽

Motor Control ◽

Caenorhabditis Elegans ◽

Neural Circuit ◽

Rhythmic Movement ◽

Circuit Model ◽

Neural Oscillators ◽

C Elegans ◽

Body Model ◽

Multicellular Organisms

The nematode Caenorhabditis elegans (C. elegans), a relatively simple organism in structure, is one of the most well-studied multicellular organisms. We developed a virtual C. elegans based on the actual organism to analyze motor control. We propose a dynamic body model, including muscles, controlled by a neural circuit model based on the actual nematode. The model uses neural oscillators to generate rhythmic movement. Computer simulation confirmed that the virtual C. elegans realizes motor control similar qualitatively to that of the actual organism. Specified classes of neurons are killed in the neural circuit model corresponding to actual unc mutants, demonstrating that resulting movement of the virtual C. elegans resembles that of actual mutants.

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Proprioceptive Coupling within Motor Neurons Drives C. elegans Forward Locomotion

Neuron ◽

10.1016/j.neuron.2012.08.039 ◽

2012 ◽

Vol 76 (4) ◽

pp. 750-761 ◽

Cited By ~ 135

Author(s):

Quan Wen ◽

Michelle D. Po ◽

Elizabeth Hulme ◽

Sway Chen ◽

Xinyu Liu ◽

...

Keyword(s):

Motor Neurons ◽

C Elegans ◽

Forward Locomotion

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The Atypical Rho GTPase CHW-1 Works With SAX-3/Robo to Mediate Axon Guidance in Caenorhabditis elegans

10.1101/265066 ◽

2018 ◽

Cited By ~ 1

Author(s):

Jamie K. Alan ◽

Sara Robinson ◽

Katie Magsig ◽

Rafael S. Demarco ◽

Erik A. Lundquist

Keyword(s):

Caenorhabditis Elegans ◽

Axon Guidance ◽

Motor Neurons ◽

Rho Gtpases ◽

Rho Gtpase ◽

Genetic Interaction ◽

Small Gtpases ◽

Axon Pathfinding ◽

Rho Proteins ◽

C Elegans

AbstractDuring development, neuronal cells extend an axon towards their target destination in response to a cue to form a properly functioning nervous system. Rho proteins, Ras-related small GTPases that regulate cytoskeletal organization and dynamics, cell adhesion, and motility, are known to regulate axon guidance. Despite extensive knowledge about canonical Rho proteins (RhoA/Rac1/Cdc42), little is known about the Caenorhabditis elegans (C. elegans) atypical Cdc42-like family members CHW-1 and CRP-1 in regards to axon pathfinding and neuronal migration. chw-1(Chp/Wrch) encodes a protein that resembles human Chp (Wrch-2/RhoV) and Wrch-1 (RhoU), and crp-1 encodes for a protein that resembles TC10 and TCL. Here, we show that chw-1 works redundantly with crp-1 and cdc-42 in axon guidance. Furthermore, proper levels of chw-1 expression and activity are required for proper axon guidance. When examining CHW-1 GTPase mutants, we found that the native CHW-1 protein is likely partially activated, and mutations at a conserved residue (position 12 using Ras numbering, position 18 in CHW-1) alter axon guidance and neural migration. Additionally, we showed that chw-1 genetically interacts with the guidance receptor sax-3 in PDE neurons. Finally, in VD/DD motor neurons, chw-1 works downstream of sax-3 to control axon guidance. In summary, this is the first study implicating the atypical Rho GTPases chw-1 and crp-1 in axon guidance. Furthermore, this is the first evidence of genetic interaction between chw-1 and the guidance receptor sax-3. These data suggest that chw-1 is likely acting downstream and/or in parallel to sax-3 in axon guidance.

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