Abstract
Innate social behaviours emerge from neuronal circuits that interpret sensory information on the basis of an individual’s own genotype, sex and experience. The regulated aggregation behaviour of the nematode Caenorhabditis elegans, a simple animal with only 302 neurons, is an attractive system to analyse these circuits. Wild social strains of C. elegans aggregate in the presence of specific sensory cues, but solitary strains do not1,2,3,4. Here we identify the RMG inter/motor neuron as the hub of a regulated circuit that controls aggregation and related behaviours. RMG is the central site of action of the neuropeptide receptor gene npr-1, which distinguishes solitary strains (high npr-1 activity) from wild social strains (low npr-1 activity); high RMG activity is essential for all aspects of social behaviour. Anatomical gap junctions connect RMG to several classes of sensory neurons known to promote aggregation, and to ASK sensory neurons, which are implicated in male attraction to hermaphrodite pheromones5. We find that ASK neurons respond directly to pheromones, and that high RMG activity enhances ASK responses in social strains, causing hermaphrodite attraction to pheromones at concentrations that repel solitary hermaphrodites. The coordination of social behaviours by RMG suggests an anatomical hub-and-spoke model for sensory integration in aggregation, and points to functions for related circuit motifs in the C. elegans wiring diagram.
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References
Hodgkin, J. & Doniach, T. Natural variation and copulatory plug formation in Caenorhabditis elegans . Genetics 146, 149–164 (1997)
de Bono, M. & Bargmann, C. I. Natural variation in a neuropeptide Y receptor homolog modifies social behavior and food response in C. elegans . Cell 94, 679–689 (1998)
de Bono, M., Tobin, D. M., Davis, M. W., Avery, L. & Bargmann, C. I. Social feeding in Caenorhabditis elegans is induced by neurons that detect aversive stimuli. Nature 419, 899–903 (2002)
Gray, J. M. et al. Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue. Nature 430, 317–322 (2004)
Srinivasan, J. et al. A blend of small molecules regulates both mating and development in Caenorhabditis elegans . Nature 454, 1115–1118 (2008)
Rogers, C. et al. Inhibition of Caenorhabditis elegans social feeding by FMRFamide-related peptide activation of NPR-1. Nature Neurosci. 6, 1178–1185 (2003)
Hammock, E. A. & Young, L. J. Oxytocin, vasopressin and pair bonding: implications for autism. Phil. Trans. R. Soc. Lond. B 361, 2187–2198 (2006)
Cheung, B. H., Cohen, M., Rogers, C., Albayram, O. & de Bono, M. Experience-dependent modulation of C. elegans behavior by ambient oxygen. Curr. Biol. 15, 905–917 (2005)
Davies, A. G., Bettinger, J. C., Thiele, T. R., Judy, M. E. & McIntire, S. L. Natural variation in the npr-1 gene modifies ethanol responses of wild strains of C. elegans . Neuron 42, 731–743 (2004)
Coates, J. C. & de Bono, M. Antagonistic pathways in neurons exposed to body fluid regulate social feeding in Caenorhabditis elegans . Nature 419, 925–929 (2002)
Plummer, M. R., Rittenhouse, A., Kanevsky, M. & Hess, P. Neurotransmitter modulation of calcium channels in rat sympathetic neurons. J. Neurosci. 11, 2339–2348 (1991)
Toth, P. T., Bindokas, V. P., Bleakman, D., Colmers, W. F. & Miller, R. J. Mechanism of presynaptic inhibition of neuropeptide Y at sympathetic nerve terminals. Nature 364, 635–639 (1993)
White, J. G., Southgate, E., Thomson, J. N. & Brenner, S. The structure of the nervous system of Caenorhabditis elegans . Phil. Trans. R. Soc. Lond. B 314, 1–340 (1986)
Bargmann, C. I., Thomas, J. H. & Horvitz, H. R. Chemosensory cell function in the behavior and development of Caenorhabditis elegans . Cold Spring Harb. Symp. Quant. Biol. 55, 529–538 (1990)
Schackwitz, W. S., Inoue, T. & Thomas, J. H. Chemosensory neurons function in parallel to mediate a pheromone response in C. elegans . Neuron 17, 719–728 (1996)
Komatsu, H., Mori, I., Rhee, J. S., Akaike, N. & Ohshima, Y. Mutations in a cyclic nucleotide-gated channel lead to abnormal thermosensation and chemosensation in C. elegans . Neuron 17, 707–718 (1996)
Schiavo, G. et al. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 359, 832–835 (1992)
Chang, A. J., Chronis, N., Karow, D. S., Marletta, M. A. & Bargmann, C. I. A distributed chemosensory circuit for oxygen preference in C. elegans . PLoS Biol. 4, e274 (2006)
Sieburth, D. et al. Systematic analysis of genes required for synapse structure and function. Nature 436, 510–517 (2005)
Sieburth, D., Madison, J. M. & Kaplan, J. M. PKC-1 regulates secretion of neuropeptides. Nature Neurosci. 10, 49–57 (2007)
Okochi, Y., Kimura, K. D., Ohta, A. & Mori, I. Diverse regulation of sensory signaling by C. elegans nPKC-epsilon/eta TTX-4. EMBO J. 24, 2127–2137 (2005)
White, J. Q. et al. The sensory circuitry for sexual attraction in C. elegans males. Curr. Biol. 17, 1847–1857 (2007)
Butcher, R. A., Fujita, M., Schroeder, F. C. & Clardy, J. Small-molecule pheromones that control dauer development in Caenorhabditis elegans . Nature Chem. Biol. 3, 420–422 (2007)
Butcher, R. A., Ragains, J. R., Kim, E. & Clardy, J. A potent dauer pheromone component in Caenorhabditis elegans acts synergistically with other components. Proc. Natl Acad. Sci. USA 105, 14288–14292 (2008)
Nakai, J., Ohkura, M. & Imoto, K. A high signal-to-noise Ca2+ probe composed of a single green fluorescent protein. Nature Biotechnol. 19, 137–141 (2001)
Chalasani, S. H. et al. Dissecting a circuit for olfactory behaviour in Caenorhabditis elegans . Nature 450, 63–70 (2007)
Suzuki, H. et al. Functional asymmetry in Caenorhabditis elegans taste neurons and its computational role in chemotaxis. Nature 454, 114–117 (2008)
Ribelayga, C., Cao, Y. & Mangel, S. C. The circadian clock in the retina controls rod-cone coupling. Neuron 59, 790–801 (2008)
Chen, B. L., Hall, D. H. & Chklovskii, D. B. Wiring optimization can relate neuronal structure and function. Proc. Natl Acad. Sci. USA 103, 4723–4728 (2006)
Ramot, D., Johnson, B. E., Berry, T. L., 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)
Brenner, S. The genetics of Caenorhabditis elegans . Genetics 77, 71–94 (1974)
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)
Kim, K. & Li, C. Expression and regulation of an FMRFamide-related neuropeptide gene family in Caenorhabditis elegans . J. Comp. Neurol. 475, 540–550 (2004)
Sweeney, S. T., Broadie, K., Keane, J., Niemann, H. & O’Kane, C. J. Targeted expression of tetanus toxin light chain in Drosophila specifically eliminates synaptic transmission and causes behavioral defects. Neuron 14, 341–351 (1995)
Hart, A. C. et al. The Wormbook: Behavior <http://www.wormbook.org/chapters/www_behavior/behavior.html> (2006)
Bargmann, C. I. & Horvitz, H. R. Chemosensory neurons with overlapping functions direct chemotaxis to multiple chemicals in C. elegans . Neuron 7, 729–742 (1991)
Hilliard, M. A., Bargmann, C. I. & Bazzicalupo, P. C. elegans responds to chemical repellents by integrating sensory inputs from the head and the tail. Curr. Biol. 12, 730–734 (2002)
Bargmann, C. I. & Avery, L. Laser killing of cells in Caenorhabditis elegans . Methods Cell Biol. 48, 225–250 (1995)
Hilliard, M. A. et al. In vivo imaging of C. elegans ASH neurons: cellular response and adaptation to chemical repellants. EMBO J. 24, 63–72 (2005)
Ward, A., Liu, J., Feng, Z. & Xu, X. Z. Light-sensitive neurons and channels mediate phototaxis in C. elegans . Nature Neurosci. 11, 916–922 (2008)
Acknowledgements
We thank L. Looger for GCaMP2.2b, M. Nonet for cleavage-resistant synaptobrevin, and J. Ragains for synthesizing ascarosides. This work was funded by the Howard Hughes Medical Institute, the Harold and Leila Y Mathers Charitable Foundation, the Jensam Foundation, and National Institute of Health grants GM07739 (E.Z.M. and E.H.F.), CA24487 (J.C.) and GM077943 (R.A.B.). C.I.B. is an Investigator of the Howard Hughes Medical Institute.
Author Contributions E.Z.M. performed experiments; N.P., E.H.F., S.C., R.A.B. and J.C. developed experimental methods and reagents; E.Z.M. and C.I.B. designed and interpreted experiments and wrote the paper.
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Macosko, E., Pokala, N., Feinberg, E. et al. A hub-and-spoke circuit drives pheromone attraction and social behaviour in C. elegans. Nature 458, 1171–1175 (2009). https://doi.org/10.1038/nature07886
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DOI: https://doi.org/10.1038/nature07886
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