Drosophila show innate olfactory-driven behaviours that are observed in naive animals without previous learning or experience, suggesting that the neural circuits that mediate these behaviours are genetically programmed. Despite the numerical simplicity of the fly nervous system, features of the anatomical organization of the fly brain often confound the delineation of these circuits. Here we identify a neural circuit responsive to cVA, a pheromone that elicits sexually dimorphic behaviours1,2,3,4. We have combined neural tracing using an improved photoactivatable green fluorescent protein (PA-GFP) with electrophysiology, optical imaging and laser-mediated microlesioning to map this circuit from the activation of sensory neurons in the antennae to the excitation of descending neurons in the ventral nerve cord. This circuit is concise and minimally comprises four neurons, connected by three synapses. Three of these neurons are overtly dimorphic and identify a male-specific neuropil that integrates inputs from multiple sensory systems and sends outputs to the ventral nerve cord. This neural pathway suggests a means by which a single pheromone can elicit different behaviours in the two sexes.
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Ejima, A. et al. Generalization of courtship learning in Drosophila is mediated by cis-vaccenyl acetate. Curr. Biol. 17, 599–605 (2007)
Kurtovic, A., Widmer, A. & Dickson, B. J. A single class of olfactory neurons mediates behavioural responses to a Drosophila sex pheromone. Nature 446, 542–546 (2007)
Billeter, J. C., Atallah, J., Krupp, J. J., Millar, J. G. & Levine, J. D. Specialized cells tag sexual and species identity in Drosophila melanogaster . Nature 461, 987–991 (2009)
Wang, L. & Anderson, D. J. Identification of an aggression-promoting pheromone and its receptor neurons in Drosophila . Nature 463, 227–231 (2010)
Bartelt, R. J., Schaner, A. M. & Jackson, L. L. Cis-vaccenyl acetate as an aggregation pheromone in Drosophila melanogaster . J. Chem. Ecol. 11, 1747–1756 (1985)
Clyne, P., Grant, A., O'Connell, R. & Carlson, J. R. Odorant response of individual sensilla on the Drosophila antenna. Invert. Neurosci. 3, 127–135 (1997)
van der Goes van Naters, W. & Carlson, J. R. Receptors and neurons for fly odors in Drosophila . Curr. Biol. 17, 606–612 (2007)
Couto, A., Alenius, M. & Dickson, B. J. Molecular, anatomical, and functional organization of the Drosophila olfactory system. Curr. Biol. 15, 1535–1547 (2005)
Fishilevich, E. & Vosshall, L. B. Genetic and functional subdivision of the Drosophila antennal lobe. Curr. Biol. 15, 1548–1553 (2005)
Marin, E. C., Jefferis, G. S., Komiyama, T., Zhu, H. & Luo, L. Representation of the glomerular olfactory map in the Drosophila brain. Cell 109, 243–255 (2002)
Wong, A. M., Wang, J. W. & Axel, R. Spatial representation of the glomerular map in the Drosophila protocerebrum. Cell 109, 229–241 (2002)
Jefferis, G. S. et al. Comprehensive maps of Drosophila higher olfactory centers: spatially segregated fruit and pheromone representation. Cell 128, 1187–1203 (2007)
Datta, S. R. et al. The Drosophila pheromone cVA activates a sexually dimorphic neural circuit. Nature 452, 473–477 (2008)
Stockinger, P., Kvitsiani, D., Rotkopf, S., Tirian, L. & Dickson, B. J. Neural circuitry that governs Drosophila male courtship behavior. Cell 121, 795–807 (2005)
Manoli, D. S. et al. Male-specific fruitless specifies the neural substrates of Drosophila courtship behaviour. Nature 436, 395–400 (2005)
Kimura, K., Ote, M., Tazawa, T. & Yamamoto, D. Fruitless specifies sexually dimorphic neural circuitry in the Drosophila brain. Nature 438, 229–233 (2005)
Kimura, K., Hachiya, T., Koganezawa, M., Tazawa, T. & Yamamoto, D. Fruitless and doublesex coordinate to generate male-specific neurons that can initiate courtship. Neuron 59, 759–769 (2008)
Ryner, L. C. et al. Control of male sexual behavior and sexual orientation in Drosophila by the fruitless gene. Cell 87, 1079–1089 (1996)
Demir, E. & Dickson, B. J. fruitless splicing specifies male courtship behavior in Drosophila . Cell 121, 785–794 (2005)
Vrontou, E., Nilsen, S. P., Demir, E., Kravitz, E. A. & Dickson, B. J. fruitless regulates aggression and dominance in Drosophila . Nature Neurosci. 9, 1469–1471 (2006)
Billeter, J. C. et al. Isoform-specific control of male neuronal differentiation and behavior in Drosophila by the fruitless gene. Curr. Biol. 16, 1063–1076 (2006)
Chan, Y. B. & Kravitz, E. A. Specific subgroups of FruM neurons control sexually dimorphic patterns of aggression in Drosophila melanogaster . Proc. Natl Acad. Sci. USA 104, 19577–19582 (2007)
Patterson, G. H. & Lippincott-Schwartz, J. A photoactivatable GFP for selective photolabeling of proteins and cells. Science 297, 1873–1877 (2002)
Shaner, N. C., Patterson, G. H. & Davidson, M. W. Advances in fluorescent protein technology. J. Cell Sci. 120, 4247–4260 (2007)
Kazama, H. & Wilson, R. I. Homeostatic matching and nonlinear amplification at identified central synapses. Neuron 58, 401–413 (2008)
Schlief, M. L. & Wilson, R. I. Olfactory processing and behavior downstream from highly selective receptor neurons. Nature Neurosci. 10, 623–630 (2007)
Tian, L. et al. Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. Nature Methods 6, 875–881 (2009)
Dulac, C. & Kimchi, T. Neural mechanisms underlying sex-specific behaviors in vertebrates. Curr. Opin. Neurobiol. 17, 675–683 (2007)
Clyne, J. D. & Miesenbock, G. Sex-specific control and tuning of the pattern generator for courtship song in Drosophila . Cell 133, 354–363 (2008)
Crameri, A., Whitehorn, E. A., Tate, E. & Stemmer, W. P. Improved green fluorescent protein by molecular evolution using DNA shuffling. Nature Biotechnol. 14, 315–331 (1996)
Pedelacq, J. D., Cabantous, S., Tran, T., Terwilliger, T. C. & Waldo, G. S. Engineering and characterization of a superfolder green fluorescent protein. Nature Biotechnol. 24, 79–88 (2006)
Stocker, R. F., Heimbeck, G., Gendre, N. & de Belle, J. S. Neuroblast ablation in Drosophila P[GAL4] lines reveals origins of olfactory interneurons. J. Neurobiol. 32, 443–456 (1997)
Ito, K. et al. The organization of extrinsic neurons and their implications in the functional roles of the mushroom bodies in Drosophila melanogaster Meigen. Learn. Mem. 5, 52–77 (1998)
We thank T. Jessell, C. Zuker and members of the Axel laboratory for discussion and comments on this manuscript; J. Flores for technical assistance; B. Dickson for reagents; P. Kisloff for assistance in the preparation of this manuscript; and M. Gutierrez and A. Nemes for general laboratory support. This work was funded in part by a grant from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative. Further financial support was provided by the Helen Hay Whitney Foundation (V.R. and S.R.D.), the Burroughs Welcome Fund (S.R.D.) and the Howard Hughes Medical Institute (R.A. and L.L.L.).
The authors declare no competing financial interests.
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Ruta, V., Datta, S., Vasconcelos, M. et al. A dimorphic pheromone circuit in Drosophila from sensory input to descending output. Nature 468, 686–690 (2010). https://doi.org/10.1038/nature09554
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