RESEARCH ARTICLE An hourglass circuit motif transforms a motor program via subcellularly localized muscle calcium signaling and contraction Steven R Sando1, Nikhil Bhatla1,2,3, Eugene LQ Lee1,3, H Robert Horvitz1* 1Howard Hughes Medical Institute, Department of Biology, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, United States; 2Miller Institute, Helen Wills Neuroscience Institute, Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, United States; 3Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States 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. *For correspondence:
[email protected] Competing interests: The Introduction authors declare that no How animal nervous systems differentially control muscle contractions to generate the variety of flex- competing interests exist. ible, context-appropriate behaviors necessary for survival and reproduction is a fundamental prob- Funding: See page 29 lem in neuroscience.