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A hub-and-spoke circuit drives pheromone attraction and social behaviour in C. elegans

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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Figure 1: Selective expression of NPR-1 suppresses aggregation and related behaviours in npr-1 mutants.
Figure 2: Inhibition of RMG by NPR-1 suppresses social behaviour.
Figure 3: ASK and ASJ sensory neurons promote aggregation.
Figure 4: Behavioural and neuronal responses to pheromones.

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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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Correspondence to Cornelia I. Bargmann.

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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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