Intestinal calcium waves coordinate a behavioral motor program in C. elegans

Abstract

Periodic behavioral motor patterns are normally controlled by neural circuits, such as central pattern generators. We here report a novel mechanism of motor pattern generation by non-neural cells. The defecation motor program in Caenorhabditis elegans consists of three stereotyped motor steps with precise timing and this behavior has been studied as a model system of a ultradian biological clock [J.H. Thomas, Genetic analysis of defecation in C. elegans, Genetics 124 (1990) 855–872; D.W. Liu, J.H. Thomas, Regulation of a periodic motor program in C. elegans, J. Neurosci. 14 (1994) 1953–1962; K. Iwasaki, D.W. Liu, J.H. Thomas, Genes that control a temperature-compensated ultradian clock in Caenorhabditis elegans, Proc. Natl. Acad. Sci. USA 92 (1995), 10317–10321]. It was previously implied that the inositol-1,4,5-trisphosphate (IP3) receptor in the intestine was necessary for this periodic behavior [P. Dal Santo, M.A. Logan, A.D. Chisholm, E.M. Jorgensen, The inositol trisphosphate receptor regulates a 50 s behavioral rhythm in C. elegans, Cell 98 (1999) 757–767]. Therefore, we developed a new assay system to study a relationship between this behavioral timing and intestinal Ca 2+ dynamics. Using this assay system, we found that the timing between the first and second motor steps is coordinated by intercellular Ca 2+-wave propagation in the intestine. Lack of the Ca 2+-wave propagation correlated with no coordination of the motor steps in the CaMKII mutant. Also, when the Ca 2+-wave propagation was blocked by the IP3 receptor inhibitor heparin at the mid-intestine in wild type, the second/third motor steps were eliminated, which phenocopied ablation of the motor neurons AVL and DVB. These observations suggest that an intestinal Ca 2+-wave propagation governs the timing of neural activities that controls specific behavioral patterns in C. elegans.