An extrasynaptic GABAergic signal modulates a pattern of forward movement in Caenorhabditis elegans.

Yu Shen,Quan Wen,He Liu,Yuqi Qin,Tianqi Xu,Gareth Harris,Taizo Kawano,Yun Zhang,Min Wu,Aravinthan Dt Samuel,Connie Zhong

doi:10.7554/elife.14197

Abstract

As a common neurotransmitter in the nervous system, γ-aminobutyric acid (GABA) modulates locomotory patterns in both vertebrates and invertebrates. However, the signaling mechanisms underlying the behavioral effects of GABAergic modulation are not completely understood. Here, we demonstrate that a GABAergic signal in C. elegans modulates the amplitude of undulatory head bending through extrasynaptic neurotransmission and conserved metabotropic receptors. We show that the GABAergic RME head motor neurons generate undulatory activity patterns that correlate with head bending and the activity of RME causally links with head bending amplitude. The undulatory activity of RME is regulated by a pair of cholinergic head motor neurons SMD, which facilitate head bending, and inhibits SMD to limit head bending. The extrasynaptic neurotransmission between SMD and RME provides a gain control system to set head bending amplitude to a value correlated with optimal efficiency of forward movement.

Highlights

In both vertebrates and invertebrates, neuromodulators profoundly shape the activity of neural circuits, giving rise to organized and yet flexible patterns of output (Bargmann and Marder, 2013)
Similar groups of anterior muscle cells are innervated by four GABAergic RME motor neurons, RMED (Dorsal), RMEV (Ventral), RMEL (Left), and RMER (Right) that innervate the contralateral muscles in the ventral, dorsal, right, and left quadrants, respectively (Figure 1A) (McIntire et al, 1993b; White et al, 1986)
We found that the operated animals still made undulatory head bending and forward movement, suggesting that the RME GABAergic neurons are not required for the generation of the movements

Summary

Introduction

In both vertebrates and invertebrates, neuromodulators profoundly shape the activity of neural circuits, giving rise to organized and yet flexible patterns of output (Bargmann and Marder, 2013). Among a large number of neuromodulators, GABA, a major inhibitory neurotransmitter found in all nervous systems, plays a critical role in modulating locomotory patterns by regulating the underlying neural circuits at multiple levels (Tegner et al, 1993; Cazalets et al, 1998; Reith and Sillar, 1999; Swensen et al, 2000; Ziskind-Conhaim, 2013; Fidelin et al, 2015). A great deal is known about the modulatory role of GABA in regulating locomotory patterns. All the stomatogastric neurons respond to GABA with either an excitatory or inhibitory effect (Swensen et al, 2000), which are likely to contribute to the diverse motor patterns that can be generated by the stomatogastric system. The modulatory role of GABA has been characterized in the spinal motor networks, where reciprocal glycinergic inhibition between contralateral and antagonist neuronal pools gives

Methods

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Conclusion