Proprioceptive Coupling within Motor Neurons Drives C. Elegans Forward Locomotion

Locomotion requires coordinated motor activity throughout an animal’s body. In both vertebrates and invertebrates, chains of coupled central pattern generators (CPGs) are commonly evoked to explain local rhythmic behaviors. In C. elegans, we report that proprioception within the motor circuit is responsible for propagating and coordinating rhythmic undulatory waves from head to tail during forward movement. Proprioceptive coupling between adjacent body regions transduces rhythmic movement initiated near the head into bending waves driven along the body by a chain of reflexes. Using optogenetics and calcium imaging to manipulate and monitor motor circuit activity of moving C. elegans held in microfluidic devices, we found that the B-type cholinergic motor neurons transduce the proprioceptive signal. In C. elegans, a sensorimotor feedback loop operating within a specific type of motor neuron both drives and organizes body movement.Chemistry and Chemical BiologyPhysic

Information flow through a model of the C. elegans klinotaxis circuit

Understanding how information about external stimuli is transformed into behavior is one of the central goals of neuroscience. Here we characterize the information flow through a complete sensorimotor circuit: from stimulus, to sensory neurons, to interneurons, to motor neurons, to muscles, to motion. Specifically, we apply a recently developed framework for quantifying information flow to a previously published ensemble of models of salt klinotaxis in the nematode worm C. elegans. The models are grounded in the neuroanatomy and currently known neurophysiology of the worm. The unknown model parameters were optimized to reproduce the worm's behavior. Information flow analysis reveals several key principles underlying how the models operate: (1) Interneuron class AIY is responsible for integrating information about positive and negative changes in concentration, and exhibits a strong left/right information asymmetry. (2) Gap junctions play a crucial role in the transfer of information responsible for the information symmetry observed in interneuron class AIZ. (3) Neck motor neuron class SMB implements an information gating mechanism that underlies the circuit's state-dependent response. (4) The neck carries non-uniform distribution about changes in concentration. Thus, not all directions of movement are equally informative. Each of these findings corresponds to an experimental prediction that could be tested in the worm to greatly refine our understanding of the neural circuit underlying klinotaxis. Information flow analysis also allows us to explore how information flow relates to underlying electrophysiology. Despite large variations in the neural parameters of individual circuits, the overall information flow architecture circuit is remarkably consistent across the ensemble, suggesting that information flow analysis captures general principles of operation for the klinotaxis circuit

Gait Modulation in C. elegans: An Integrated Neuromechanical Model

Equipped with its 302-cell nervous system, the nematode Caenorhabditis elegans adapts its locomotion in different environments, exhibiting so-called swimming in liquids and crawling on dense gels. Recent experiments have demonstrated that the worm displays the full range of intermediate behaviors when placed in intermediate environments. The continuous nature of this transition strongly suggests that these behaviors all stem from modulation of a single underlying mechanism. We present a model of C. elegans forward locomotion that includes a neuromuscular control system that relies on a sensory feedback mechanism to generate undulations and is integrated with a physical model of the body and environment. We find that the model reproduces the entire swim-crawl transition, as well as locomotion in complex and heterogeneous environments. This is achieved with no modulatory mechanism, except via the proprioceptive response to the physical environment. Manipulations of the model are used to dissect the proposed pattern generation mechanism and its modulation. The model suggests a possible role for GABAergic D-class neurons in forward locomotion and makes a number of experimental predictions, in particular with respect to non-linearities in the model and to symmetry breaking between the neuromuscular systems on the ventral and dorsal sides of the body

Experimental And Computational Analyses Of Locomotor Rhythm Generation And Modulation In Caenorhabditis Elegans

Neural circuits coordinate with muscles and sensory feedback to generate motor behaviors appropriate to its natural environment. Studying mechanisms underlying complex organism locomotion has been challenging, partly due to the complexity of their nervous systems. Here, I used the roundworm C. elegans to understand the locomotor circuit. With its well-mapped nervous system, easily-measurable movements, genetic manipulability, and many human homologous genes, C. elegans has been commonly used as a model organism for dissecting the circuit, cellular, and molecular principles of locomotion. My work introduces two separate approaches to probe the mechanisms by which the C. elegans motor circuit generates and modulates undulations. First, I quantified C. elegans movements during free locomotion and during transient muscle inhibition. Undulations were asymmetrical with respect to the duration of bending and unbending per cycle. Phase response curves induced by brief optogenetic head muscle inhibitions showed gradual increases and rapid decreases as a function of phase at which the perturbation was applied. A relaxation oscillator model was developed based on proprioceptive thresholds that switch the active muscle moment. It quantitatively agrees with data from free movement, phase responses, and previous results for gait adaptation to mechanical loads. Next, I characterized a proprioception-mediated compensatory behavior during C. elegans forward locomotion: the anterior body bending amplitude compensates for the change in midbody bending amplitude by an opposing homeostatic response. I demonstrated that curvature compensation requires dopamine signaling driven by PDE neurons. Calcium imaging experiments suggested a proprioceptive functionality for PDE in sensing midbody curvature. Downstream of PDE dopamine signaling, curvature compensation requires D2-like dopamine receptor DOP-3 in the interneurons AVK. FMRFamide-like neuropeptide FLP-1, released by AVK, regulates SMB motor neurons via receptor NPR-6 to modulate anterior bending amplitude. These results revealed a mechanism whereby proprioception works with dopamine and neuropeptide signaling to mediate homeostatic locomotor control. Together, through a consolidation of experimental and computational approaches, I found C. elegans utilizes its circuitry not only to act motor behaviors but to adjust/correct its ongoing behaviors in its natural contexts

Modeling the chemotaxis behaviors of C. Elegans using neural network: from artificial to biological approach

Ph.DDOCTOR OF PHILOSOPH

Signatures of proprioceptive control in Caenorhabditis elegans locomotion

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’