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

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.

Download Full-text

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

Download Full-text

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.

Download Full-text

Distributed Rhythm Generators Underlie Caenorhabditis elegans Forward Locomotion

10.1101/141911 ◽

2017 ◽

Cited By ~ 1

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

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.

Download Full-text

From head to tail: a neuromechanical model of forward locomotion in Caenorhabditis elegans

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2017.0374 ◽

2018 ◽

Vol 373 (1758) ◽

pp. 20170374 ◽

Cited By ~ 5

Author(s):

Eduardo J. Izquierdo ◽

Randall D. Beer

Keyword(s):

Caenorhabditis Elegans ◽

Biomechanical Model ◽

Neural Model ◽

Cellular Level ◽

The Body ◽

Rhythmic Pattern ◽

Unknown Parameters ◽

Forward Movement ◽

C Elegans ◽

Forward Locomotion

With 302 neurons and a near-complete reconstruction of the neural and muscle anatomy at the cellular level, Caenorhabditis elegans is an ideal candidate organism to study the neuromechanical basis of behaviour. Yet despite the breadth of knowledge about the neurobiology, anatomy and physics of C. elegans , there are still a number of unanswered questions about one of its most basic and fundamental behaviours: forward locomotion. How the rhythmic pattern is generated and propagated along the body is not yet well understood. We report on the development and analysis of a model of forward locomotion that integrates the neuroanatomy, neurophysiology and body mechanics of the worm. Our model is motivated by experimental analysis of the structure of the ventral cord circuitry and the effect of local body curvature on nearby motoneurons. We developed a neuroanatomically grounded model of the head motoneuron circuit and the ventral nerve cord circuit. We integrated the neural model with an existing biomechanical model of the worm's body, with updated musculature and stretch receptors. Unknown parameters were evolved using an evolutionary algorithm to match the speed of the worm on agar. We performed 100 evolutionary runs and consistently found electrophysiological configurations that reproduced realistic control of forward movement. The ensemble of successful solutions reproduced key experimental observations that they were not designed to fit, including the wavelength and frequency of the propagating wave. Analysis of the ensemble revealed that head motoneurons SMD and RMD are sufficient to drive dorsoventral undulations in the head and neck and that short-range posteriorly directed proprioceptive feedback is sufficient to propagate the wave along the rest of the body. This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling C. elegans at cellular resolution’.

Download Full-text

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.

Download Full-text

ENU-3 is a novel outgrowth and guidance protein in c. elegans

10.32920/ryerson.14658099 ◽

2021 ◽

Author(s):

Callista Stephanie Yee

Keyword(s):

Amino Acids ◽

Nervous System ◽

Caenorhabditis Elegans ◽

Membrane Protein ◽

Motor Neuron ◽

Gene Product ◽

Motor Neurons ◽

Growth Cones ◽

C Elegans ◽

Extracellular Molecules

During the development of the nervous system, the migration of many cells and axons is guided by extracellular molecules. These molecules bind to receptors at the tips of the growth cones of migrating axons and trigger intracellular signalling to steer the axons along the correct trajectories. Previous work has identified a novel mutant, enu-3 (enhancer of Unc), that enhances the motor neuron axon outgrowth defects observed in strains of Caenorhabditis elegans that lack either the UNC-5 receptor or its ligand UNC-6/Netrin, enu-3 single mutants have weak motor neuron axon migration defects. Both outgrowth defects of double mutants and axon migration defects of enu-3 mutants were rescued by expression of the H04D03.1 gene product. Enu-3/H04D03.1 encodes a novel predicted putative trans-membrane protein of 204 amino acids. ENU-3 is expressed weakly expressed in many cell bodies along the ventral cord, including those of the DA and DB motor neurons.

Download Full-text

ENU-3 is a novel outgrowth and guidance protein in c. elegans

10.32920/ryerson.14658099.v1 ◽

2021 ◽

Author(s):

Callista Stephanie Yee

Keyword(s):

Amino Acids ◽

Nervous System ◽

Caenorhabditis Elegans ◽

Membrane Protein ◽

Motor Neuron ◽

Gene Product ◽

Motor Neurons ◽

Growth Cones ◽

C Elegans ◽

Extracellular Molecules

Download Full-text

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.

Download Full-text

Signatures of proprioceptive control in Caenorhabditis elegans locomotion

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2018.0208 ◽

2018 ◽

Vol 373 (1758) ◽

pp. 20180208 ◽

Cited By ~ 10

Author(s):

Jack E. Denham ◽

Thomas Ranner ◽

Netta Cohen

Keyword(s):

Caenorhabditis Elegans ◽

Neural Control ◽

The Body ◽

C Elegans ◽

Feed Forward Control ◽

Fundamental Relationship ◽

Phase Lags ◽

Forward Locomotion ◽

Undulatory Locomotion ◽

Mechanical Modulation

Animal neuromechanics describes the coordinated self-propelled movement of a body, subject to the combined effects of internal neural control and mechanical forces. Here we use a computational model to identify effects of neural and mechanical modulation on undulatory forward locomotion of Caenorhabditis elegans , with a focus on proprioceptively driven neural control. We reveal a fundamental relationship between body elasticity and environmental drag in determining the dynamics of the body and demonstrate the manifestation of this relationship in the context of proprioceptively driven control. By considering characteristics unique to proprioceptive neurons, we predict the signatures of internal gait modulation that contrast with the known signatures of externally or biomechanically modulated gait. We further show that proprioceptive feedback can suppress neuromechanical phase lags during undulatory locomotion, contrasting with well studied advancing phase lags that have long been a signature of centrally generated, feed-forward control. This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling C. elegans at cellular resolution’.

Download Full-text

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

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2017.0370 ◽

2018 ◽

Vol 373 (1758) ◽

pp. 20170370 ◽

Cited By ~ 12

Author(s):

Quan Wen ◽

Shangbang Gao ◽

Mei Zhen

Keyword(s):

Caenorhabditis Elegans ◽

Motor Neurons ◽

Central Pattern Generators ◽

Oscillatory Activity ◽

C Elegans ◽

Ventral Cord ◽

Small Neuron ◽

Motor Rhythm ◽

Pattern Generators

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’.

Download Full-text