Modular integration of neural connectomics, dynamics and biomechanics for identification of behavioral sensorimotor pathways in Caenorhabditis elegans

Abstract

Computational approaches which emulate in-vivo nervous system are needed to investigate mechanisms of the brain to orchestrate behavior. Such approaches must integrate a series of biophysical models encompassing the nervous system, muscles, biomechanics to allow observing the system in its entirety while supporting model variations. Here we develop modWorm: a modular modeling framework for the nematode C. elegans. modWorm allows for construction of a model as an integrated series of configurable, exchangeable modules each describing specific biophysical processes across different modalities. Utilizing modWorm, we propose a base neuro-mechanical model for C. elegans built upon the complete connectome. The model integrates a series of 7 modules: i) intra-cellular dynamics, ii) electrical and iii) chemical extra-cellular neural dynamics, iv) translation of neural activity to muscle calcium dynamics, v) muscle calcium dynamics to muscle forces, vi) muscle forces to body postures and vii) proprioceptive feedback. We validate the base model by in-silico injection of constant currents into neurons known to be associated with locomotion behaviors and by applying external forces to the body. Applications of in-silico neural stimuli experimentally known to modulate locomotion show that the model can recapitulate natural behavioral responses such as forward and backward locomotion as well as mid-locomotion responses such as avoidance and turns. Furthermore, through in-silico ablation surveys, the model can infer novel neural circuits involved in sensorimotor behaviors. To further dissect mechanisms of locomotion, we utilize modWorm to introduce empirical based model variations and model optimizations to elucidate their effects on simulated locomotion. Our results show that modWorm can be utilized to identify neural circuits which control, mediate and generate natural behavior.