Phase response analyses support a relaxation oscillator model of locomotor rhythm generation in Caenorhabditis elegans

Abstract

Neural circuits coordinate with muscles and sensory feedback to generate motor behaviors appropriate to an animal’s environment. In C. elegans, the mechanisms by which the motor circuit generates undulations and modulates them based on the environment are largely unclear. We quantitatively analyzed C. elegans locomotion during free movement and during transient optogenetic muscle inhibition. Undulatory movements were highly asymmetrical with respect to the duration of bending and unbending during each cycle. Phase response curves induced by brief optogenetic inhibition of head muscles showed gradual increases and rapid decreases as a function of phase at which the perturbation was applied. A relaxation oscillator model based on proprioceptive thresholds that switch the active muscle moment was developed and is shown to quantitatively agree with data from free movement, phase responses, and previous results for gait adaptation to mechanical loadings. Our results suggest a neuromuscular mechanism underlying C. elegans motor pattern generation within a compact circuit.

A proprioceptive feedback circuit drivesC. eleganslocomotor adaptation through dopamine signaling

“…In previous studies 27 we perturbed the muscular or neural activity in different body regions and analyzed the corresponding undulatory dynamics during forward locomotion. Using a laser targeting system 47,73 we applied green laser illumination (532 nm wavelength) to selected body regions of animals expressing the inhibitory opsin NpHR in body wall muscles (via the transgene Pmyo-3::NpHR ).…”

“…In C. elegans , proprioceptive information is implicated in generating locomotor rhythms 27 . It is used within the motor circuit to directly propagate the rhythmic bending activity from anterior to posterior segments during forward locomotion 51 , indicating that this form of proprioceptive feedback is required to sustain the animal’s normal locomotion.…”

“…Processing of the behavioral data from optogenetic and microfluidic experiments was performed using MATLAB custom software (MathWorks) as described in previous reports 27,73 . The normalized curvature K is the product of κ and the worm body length L derived from the length of the worm centerline.…”

“…In mammals, proprioceptive inputs from multiple sensory organs are continuously processed within spinal cord circuits to adapt motor behavior (18). In lamprey and other 3 undulatory animals, locomotion also relies on proprioceptive feedback to adjust the locomotor pattern to changes in the physical environment (19)(20)(21).…”

Hierarchical behavior control by a single class of interneurons

“…One candidate for a potential mechanosensory channel is the TRP family (54), and TRP1 is known to express in SAA neurons (55). Previous works (30,56,57) suggest that when swimming in surroundings with different mechanical loads, C. elegans exhibited gait adaptation by exploiting local proprioceptive feedback. Consistent with this view, SAA-ablated animals exhibited a large variation of undulatory period when swimming in solutions with changing viscosities (Fig.…”