Inhibition underlies fast undulatory locomotion inC. elegans

Abstract

239, Introduction 651, Discussion 1500• Conflict of interest statementThe authors declare no conflicts of interest.• Acknowledgments LD thanks her thesis committee: Farzan Nadim, Daphne Soares, Andrew Leifer, and Eric Fortune for useful discussions, encouragement, and support. JED and NC thank Thomas Ranner for useful and critical discussions. Some strains were provided by the CGC, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440).We also thank the National Bioresource Project of Japan, and the Takagi and Nakai Laboratories for providing strains. NC was funded by EPSRC (EP/J004057/1). Abstract 1Inhibition plays important roles in modulating the neural activities of sensory and motor systems 2 at different levels from synapses to brain regions. To achieve coordinated movement, motor 3 systems produce alternating contraction of antagonist muscles, whether along the body axis or 4 within and among limbs. In the nematode C. elegans, a small network involving excitatory 5 cholinergic and inhibitory GABAergic motoneurons generates the dorsoventral alternation of 6 body-wall muscles that supports undulatory locomotion. Inhibition has been suggested to be 7 necessary for backward undulation because mutants that are defective in GABA transmission 8 exhibit a shrinking phenotype in response to a harsh touch to the head, whereas wild-type animals 9 produce a backward escape response. Here, we demonstrate that the shrinking phenotype is exhibited 10 by wild-type as well as mutant animals in response to harsh touch to the head or tail, but only GABA 11 transmission mutants show slow locomotion after stimulation. Impairment of GABA transmission, 12 either genetically or optogenetically, induces lower undulation frequency and lower translocation 13 speed during crawling and swimming in both directions. The activity patterns of GABAergic 14 motoneurons are different during low and high undulation frequencies. During low undulation 15 frequency, GABAergic VD and DD motoneurons show similar activity patterns, while during high 16 undulation frequency, their activity alternate. The experimental results suggest at least three non-17 mutually exclusive roles for inhibition that could underlie fast undulatory locomotion in C. elegans, 18 which we tested with computational models: cross-inhibition or disinhibition of body-wall muscles, or 19 inhibitory reset. 20 21Significance Statement 22Inhibition serves multiple roles in the generation, maintenance, and modulation of the locomotive 23 program and supports the alternating activation of antagonistic muscles. When the locomotor 24 frequency increases, more inhibition is required. To better understand the role of inhibition in 25 locomotion, we used C. elegans as an animal model, and challenged a prevalent hypothesis that 26 cross-inhibition supports the dorsoventral alternation. We demonstrate via behavior analysis that 27 inhibition is related to speed rather than the direction of locomotion and that it is unnecessary for 28 muscle alternation during...

A neuromechanical model of multiple network rhythmic pattern generators for forward locomotion inC. elegans

“…Given the deliberate effort to remove from the model a number of components that are known to play important roles in forward locomotion for the sake of addressing a question that had not been tackled yet, the model naturally reveals discrepancies with a number of experiments. Specifically, there is evidence that: silencing A-class motor neurons does not entirely disrupt forward locomotion [87]; ablating AS does not disrupt forward locomotion entirely but leads to a ventral bias in the bending [77]; and D-class motor neurons may not be playing a role in coordinating body waves under certain conditions [20, 58]. In contrast, the multiple network rhythmic pattern generators hypothesis in this model relies on the participation of all motor neurons, including classes A, AS, and D. Although there is further experimental work that remains to delineate with precision the role of each of those neurons in forward locomotion, there is one relatively trivial way to resolve the inconsistency between the model and the hypothesis that those neurons play no substantial roles in forward locomotion: the re-introduction of proprioceptive feedback back into the model as an independent mechanism for generating reflexive rhythmic patterns.…”

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

“…Laser ablation studies have shown that the cholinergic B-type motor neurons are required for forward locomotion (Chalfie et al, 1985). The GABAergic D-type motor neurons provide dorsoventral cross-inhibition to the body wall muscles and are essential for maintaining normal wave shape and frequency during forward locomotion (Deng et al, 2020; Mclntire et al, 1993). A set of premotor interneurons (AVB, PVC, AVA, AVD, and AVE) regulate forward and reverse movements (Chalfie et al, 1988; Driscoll and Kaplan, 1997; Von Stetina et al, 2006).…”

AffordableCaenorhabditis eleganstracking system for classroom use

“…However, recent advances streamlined and made affordable the automated study and quantification of behavior in C. elegans and other organisms. For example, the Haspel lab at NJIT made use of the recently developed TIERPSY behavioral software (Avelino et al 2018) to build numerous worm tracking systems that are at once user friendly, and able to achieve levels of kinematic analysis that previously required considerably more expensive setups (Deng et al 2020).…”

“…Many systems have been developed over the years and are currently used across the world for the rapid and unbiased quantification of behavioral phenotypes. For example, we have used tracking systems in the past to compare the ability of mutant strains to transition between gaits (Vidal-Gadea et al, 2011), and Deng and colleagues to study the role of inhibition during locomotion (Deng et al, 2020, see Husson et al 2012 for a review of the use of tracking systems in C. elegans). Until recently, the automated quantification of C. elegans behavior was only feasible for a few wealthy (or specialized) labs.…”