An hourglass circuit motif transforms a motor program via subcellularly localized muscle calcium signaling and contraction.

Steven R Sando,Nikhil Bhatla,H Robert Horvitz,Eugene Lq Lee

doi:10.7554/elife.59341

Steven R Sando, Nikhil Bhatla + Show 2 more

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https://doi.org/10.7554/elife.59341

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Abstract

Neural control of muscle function is fundamental to animal behavior. Many muscles can generate multiple distinct behaviors. Nonetheless, individual muscle cells are generally regarded as the smallest units of motor control. We report that muscle cells can alter behavior by contracting subcellularly. We previously discovered that noxious tastes reverse the net flow of particles through the C. elegans pharynx, a neuromuscular pump, resulting in spitting. We now show that spitting results from the subcellular contraction of the anterior region of the pm3 muscle cell. Subcellularly localized calcium increases accompany this contraction. Spitting is controlled by an 'hourglass' circuit motif: parallel neural pathways converge onto a single motor neuron that differentially controls multiple muscles and the critical subcellular muscle compartment. We conclude that subcellular muscle units enable modulatory motor control and propose that subcellular muscle contraction is a fundamental mechanism by which neurons can reshape behavior.

Highlights

How animal nervous systems differentially control muscle contractions to generate the variety of flexible, context-appropriate behaviors necessary for survival and reproduction is a fundamental problem in neuroscience
Our results indicate that the pm1, pm2, and pm3 muscles play specialized roles in controlling pharyngeal particle flow during spitting: the pm2 and likely the pm1 muscles actively open the metastomal filter, increasing the aperture size of the anterior lumen and facilitating particle influx, while a subcellular anterior compartment of the pm3s opens the pharyngeal valve via subcellular calcium signaling, preventing the retention of ingested material and producing spitting
Consistent with our behavioral observations, lite-1 and gur-3 function together in light-induced calcium increases in pharyngeal muscle, with lite-1 playing the major role and gur-3 playing a minor role. These results indicate that lite-1 and gur-3 both contribute to light-induced spitting. lite-1 is necessary for the full response -- an increase in pumping rate, opening of the pharyngeal valve, opening of the metastomal filter, and a robust increase in pharyngeal muscle calcium -- while gur-3 is sufficient in the absence of lite-1 to produce an attenuated response -- partial opening of 398 the valve and filter and weak activation of pharyngeal muscle

Summary

Introduction

How animal nervous systems differentially control muscle contractions to generate the variety of flexible, context-appropriate behaviors necessary for survival and reproduction is a fundamental problem in neuroscience. The muscles of the human jaw and tongue control both feeding and speech, while the Drosophila wing muscles produce both flight and song (O’Sullivan et al, 2018). Such modulation of muscle function can be achieved via neuronally-mediated alteration of the amplitudes and relative timing of muscle motions (Briggman and Kristan, 2008; Marder and 36 Calabrese, 1996). We are analyzing the neuromuscular control of behavior using the C. elegans feeding organ, the pharynx, as a model neuromuscular system.

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