Animals locate and track chemoattractive gradients in the environment to find food. With its small nervous system, Caenorhabditis elegans is a good model system1,2 in which to understand how the dynamics of neural activity control this search behaviour. Extensive work on the nematode has identified the neurons that are necessary for the different locomotory behaviours underlying chemotaxis through the use of laser ablation3,4,5,6,7, activity recording in immobilized animals and the study of mutants4,5. However, we do not know the neural activity patterns in C. elegans that are sufficient to control its complex chemotactic behaviour. To understand how the activity in its interneurons coordinate different motor programs to lead the animal to food, here we used optogenetics and new optical tools to manipulate neural activity directly in freely moving animals to evoke chemotactic behaviour. By deducing the classes of activity patterns triggered during chemotaxis and exciting individual neurons with these patterns, we identified interneurons that control the essential locomotory programs for this behaviour. Notably, we discovered that controlling the dynamics of activity in just one interneuron pair (AIY) was sufficient to force the animal to locate, turn towards and track virtual light gradients. Two distinct activity patterns triggered in AIY as the animal moved through the gradient controlled reversals and gradual turns to drive chemotactic behaviour. Because AIY neurons are post-synaptic to most chemosensory and thermosensory neurons8, it is probable that these activity patterns in AIY have an important role in controlling and coordinating different taxis behaviours of the animal.
Subscribe to Journal
Get full journal access for 1 year
only $3.83 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Brenner, S. The genetics of behaviour. Br. Med. Bull. 29, 269–271 (1973)
Brenner, S. The genetics of Caenorhabditis elegans. Genetics 77, 71–94 (1974)
Tsalik, E. L. & Hobert, O. Functional mapping of neurons that control locomotory behavior in Caenorhabditis elegans. J. Neurobiol. 56, 178–197 (2003)
Iino, Y. & Yoshida, K. Parallel use of two behavioral mechanisms for chemotaxis in Caenorhabditis elegans. J. Neurosci. 29, 5370–5380 (2009)
Pierce-Shimomura, J. T., Morse, T. M. & Lockery, S. R. The fundamental role of pirouettes in Caenorhabditis elegans chemotaxis. J. Neurosci. 19, 9557–9569 (1999)
Wakabayashi, T., Kitagawa, I. & Shingai, R. Neurons regulating the duration of forward locomotion in Caenorhabditis elegans. Neurosci. Res. 50, 103–111 (2004)
Gray, J. M., Hill, J. J. & Bargmann, C. I. A circuit for navigation in Caenorhabditis elegans. Proc. Natl Acad. Sci. USA 102, 3184–3191 (2005)
White, J. G., Southgate, E., Thomson, J. N. & Brenner, S. The structure of the nervous system of the nematode Caenorhabditis elegans. Phil. Trans. R. Soc. Lond. B 314, 1–340 (1986)
Ward, S. Chemotaxis by the nematode Caenorhabditis elegans: identification of attractants and analysis of the response by use of mutants. Proc. Natl Acad. Sci. USA 70, 817–821 (1973)
Izquierdo, E. J. & Lockery, S. R. Evolution and analysis of minimal neural circuits for klinotaxis in Caenorhabditis elegans. J. Neurosci. 30, 12908–12917 (2010)
Chalasani, S. H. et al. Dissecting a circuit for olfactory behaviour in Caenorhabditis elegans. Nature 450, 63–70 (2007)
Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nature Neurosci. 8, 1263–1268 (2005)
Nagel, G. et al. Light activation of channelrhodopsin-2 in excitable cells of Caenorhabditis elegans triggers rapid behavioral responses. Curr. Biol. 15, 2279–2284 (2005)
Chow, B. Y. et al. High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature 463, 98–102 (2010)
Okazaki, A., Sudo, Y. & Takagi, S. Optical silencing of C. elegans cells with arch proton pump. PLoS ONE 7, e35370 (2012)
Guo, Z. V., Hart, A. C. & Ramanathan, S. Optical interrogation of neural circuits in Caenorhabditis elegans. Nature Methods 6, 891–896 (2009)
Leifer, A. M., Fang-Yen, C., Gershow, M., Alkema, M. J. & Samuel, A. D. T. Optogenetic manipulation of neural activity in freely moving Caenorhabditis elegans. Nature Methods 8, 147–152 (2011)
Stirman, J. N. et al. Real-time multimodal optical control of neurons and muscles in freely behaving Caenorhabditis elegans. Nature Methods 8, 153–158 (2011)
Lockery, S. R. The computational worm: spatial orientation and its neuronal basis in C. elegans. Curr. Opin. Neurobiol. 21, 782–790 (2011)
Kim, D., Park, S., Mahadevan, L. & Shin, J. H. The shallow turn of a worm. J. Exp. Biol. 214, 1554–1559 (2011)
McIntire, S. L., Jorgensen, E., Kaplan, J. & Horvitz, H. R. The GABAergic nervous system of Caenorhabditis elegans. Nature 364, 337–341 (1993)
Granato, M., Schnabel, H. & Schnabel, R. pha-1, a selectable marker for gene transfer in C. elegans. Nucleic Acids Res. 22, 1762–1763 (1994)
Edwards, S. L. et al. A novel molecular solution for ultraviolet light detection in Caenorhabditis elegans. PLoS Biol. 6, e198 (2008)
Karasawa, S., Araki, T., Nagai, T., Mizuno, H. & Miyawaki, A. Cyan-emitting and orange-emitting fluorescent proteins as a donor/acceptor pair for fluorescence resonance energy transfer. Biochem. J. 381, 307–312 (2004)
Ramot D, Johnson B. E, Berry T. L. Jr, Carnell L & Goodman M. B The parallel worm tracker: a platform for measuring average speed and drug-induced paralysis in nematodes. PLoS ONE 3, e2208 (2008)
Merzlyak, E. M. et al. Bright monomeric red fluorescent protein with an extended fluorescence lifetime. Nature Methods 4, 555–557 (2007)
Hires, S. A., Tian, L. & Looger, L. L. Reporting neural activity with genetically encoded calcium indicators. Brain Cell Biol. 36, 69–86 (2008)
Troemel, E. R., Sagasti, A. & Bargmann, C. I. Lateral signaling mediated by axon contact and calcium entry regulates asymmetric odorant receptor expression in C. elegans. Cell 99, 387–398 (1999)
Hobert, O. et al. Regulation of interneuron function in the C. elegans thermoregulatory pathway by the ttx-3 LIM homeobox gene. Neuron 19, 345–357 (1997)
Bendena, W. G. et al. A Caenorhabditis elegans allatostatin/galanin-like receptor NPR-9 inhibits local search behavior in response to feeding cues. Proc. Natl Acad. Sci. USA. 105, 1339–1342 (2008)
Tsalik, E. LIM homeobox gene-dependent expression of biogenic amine receptors in restricted regions of the C. elegans nervous system. Dev. Biol. 263, 81–102 (2003)
Chou, J. H., Bargmann, C. I. & Sengupta, P. The Caenorhabditis elegans odr-2 gene encodes a novel Ly-6-related protein required for olfaction. Genetics 157, 211–224 (2001)
Boulin, T., Etchberger, J. F. & Hobert, O. Reporter gene fusions. WormBook (2006)
We thank J. Dowling, S. Lockery, J. Lichtman, K. McCormick, A. Murray, E. O’Shea, A. Schier, B. Stern and members of the Ramanathan laboratory for discussions and comments, the Human Frontier Science Program (HFSP) Postdoctoral Fellowship (A.K.), National Science Foundation (NSF) Graduate Fellowship (C.-H.S.), NSF Career Award, Pew Scholar, Klingenstein Fellowship Award and the National Institutes of Health (NIH) Pioneer Awards (S.R.) for support.
The authors declare no competing financial interests.
This file contains Supplementary Materials and Methods, Supplementary Tables 1-2, legends for Supplementary Movies 1-11 (see separate zipped file), Supplementary References and Supplementary Figures 1-7. (PDF 2131 kb)
This file contains Supplementary Movies 1-11 (see Supplementary Information file for legends. (ZIP 11733 kb)
About this article
Cite this article
Kocabas, A., Shen, CH., Guo, Z. et al. Controlling interneuron activity in Caenorhabditis elegans to evoke chemotactic behaviour. Nature 490, 273–277 (2012). https://doi.org/10.1038/nature11431
Current Opinion in Neurobiology (2020)
Presynaptic MAST kinase controls opposing postsynaptic responses to convey stimulus valence in Caenorhabditis elegans
Proceedings of the National Academy of Sciences (2020)
PLOS Biology (2020)
Context-dependent operation of neural circuits underlies a navigation behavior inCaenorhabditis elegans
Proceedings of the National Academy of Sciences (2020)