WormBeat: A Strategy to Evaluate Pharyngeal Pumping Variability in the Nematode C. elegans

Abstract

In C. elegans, the feeding behavior of pharyngeal pumping occurs spontaneously in proportion to metabolism and in response to stimuli. Age‐ and health‐related changes in tissue morphology and function correlate with declines in the frequency of pumping. As such, pumping frequency is an established index of C. elegans “health”, and pumping changes illustrate and quantify functional decline. Timing of pharyngeal pumping is controlled by two pairs of pharyngeal motor neurons (MC and M3). Each pump cycle corresponds to the propagation of a single pharyngeal muscle action potential, initiated by MC and terminated by M3. We currently model this system with MC acting as an oscillator and synaptically linked to the pharyngeal muscle. Pumping can change by influences on the pace and regularity of the oscillator and/or of the fidelity of pharyngeal muscle response to neuronal inputs.Traditionally, this phenomenon has been reported as an occurrence frequency, describing the number of pumping events observed per unit time over a period of observation. Variation in pumping frequency within and between subjects, and the relative coarseness of this measure may interfere with the resolution of subtle treatment effects and ignores both the mechanisms for resulting effects as well as the potential significance of pumping variability.We use the recently developed ScreenChip system (NemaMetrix) to detect individual pump events, and have developed an algorithm (WormBeat) to normalize variation between subjects and distinguish variability associated with MC neuron pace and neuromuscular fidelity of the pharynx. We present the validity of our algorithm and demonstrate enhanced resolution in detecting differences in pumping behavior using simulations representing ranges and distinct sources of biologically relevant variability. This presentation describes the theory and practice of the algorithm. The use of this analysis strategy on an experimental dataset is described in a companion presentation.Support or Funding InformationWork reported in this publication was supported by the National Heart Lung and Blood Institute and National Institute of General Medical Sciences of the National Institutes of Health under Award Numbers 1R15HL126105, 1SC2GM112570, UL1GM118979, TL4GM118980, and RL5GM118978. The work is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health or any other funding body.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.