Izquierdo, Euardo J. et al. (2019) International Worm Meeting "A computational model of mixed pattern generation for forward and backward locomotion in C. elegans."

Beer, Randall D., Izquierdo, Euardo J., Olivares, Erick

[International Worm Meeting, 2019]

C. elegans locomotes in an undulatory fashion, generating thrust by propagating dorsoventral bends along its body. As in many other organisms, there are likely multiple mechanisms, external and internal, contributing to the generation, propagation, and coordination of rhythmic patterns controlling locomotion in the worm. Experimental and theoretical work in C. elegans has provided support for roles of both stretch-receptor feedback and central pattern generators. Current work leaves a number of major questions unanswered: (1) Can multiple network oscillators coordinate their activity to produce the traveling wave necessary for locomotion in the absence of stretch-receptor feedback? (2) Can stretch-receptor feedback alone drive locomotion? and (3) How can stretch-receptor feedback work together with intrinsic oscillators to modulate movement? In the current work, we integrated a neuroanatomically-grounded model of the ventral nerve cord with a biomechanical model of the worm's body and we used an evolutionary algorithm to determine unknown physiological parameters of each neuron and connection so that the complete system reproduces the kinematics of forward and backward locomotive behavior, as controlled by command interneurons. We performed experiments under three conditions: (a) stretch-receptor feedback was never available during evolution, (b) stretch-receptor feedback was always available, and (c) stretch-receptor feedback was intermittently available. We then analyzed the ensemble of solutions as a way to address the motivating questions and generate novel hypotheses about the neuromechanical basis for locomotion. In all conditions, the model worms reproduce the speed of the worm and are consistent with key kinematic features, such as frequency and wavelength. First, when stretch-receptor feedback information was not available, a chain of central pattern generators, connected through a set of chemical and gap junctions, can drive forward and backward locomotion on agar. Analysis of these solutions reveal three different possible mechanisms for realizing the anterior-posterior coordination of the intrinsic oscillators. Second, when stretch-receptor feedback information was reliably available, the neural controller takes advantage of this information to both generate and propagate the rhythmic pattern without the need for intrinsic oscillations. Finally, model worms evolved with intermittent stretch-receptor feedback utilized mixed pattern generators: a combination of multiple intrinsic oscillators capable of coordination that use sensory feedback to finetune and modulate their motor patterns. Analysis of these results suggests specific mechanisms for how stretch-receptor feedback is used to help coordinate the intrinsic oscillators.