Abstract
Drosophila melanogaster postfeeding larvae show food-averse migration toward food-free habitats before metamorphosis. This developmental switching from food attraction to aversion is regulated by a neuropeptide Y (NPY)-related brain signaling peptide. We used the fly larva model to delineate the neurobiological basis of age-restricted response to environmental stimuli. Here we provide evidence for a fructose-responsive chemosensory pathway that modulates food-averse migratory and social behaviors. We found that fructose potently elicited larval food-averse behaviors, and painless (pain), a transient receptor potential channel that is responsive to noxious stimuli, was required for the fructose response. A subset of pain-expressing sensory neurons have been identified that show pain-dependent excitation by fructose. Although evolutionarily conserved avoidance mechanisms are widely appreciated for their roles in stress coping and survival, their biological importance in animal physiology and development remains unknown. Our findings demonstrate how an avoidance mechanism is recruited to facilitate animal development.
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References
Sokolowski, M.B. NPY and the regulation of behavioral development. Neuron 39, 6–8 (2003).
Bolhuis, J.J. & Gahr, M. Neural mechanisms of birdsong memory. Nat. Rev. Neurosci. 7, 347–357 (2006).
Wu, Q. et al. Developmental control of foraging and social behavior by the Drosophila neuropeptide Y-like system. Neuron 39, 147–161 (2003).
Chiang, H.C.H.A.G. An analytical study of population growth in Drosophila melanogaster. Ecol. Monogr. 20, 173–206 (1950).
Ashburner, M. Drosophila (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1989).
Thorsell, A. & Heilig, M. Diverse functions of neuropeptide Y revealed using genetically modified animals. Neuropeptides 36, 182–193 (2002).
Brumovsky, P., Shi, T.S., Landry, M., Villar, M.J. & Hokfelt, T. Neuropeptide tyrosine and pain. Trends Pharmacol. Sci. 28, 93–102 (2007).
McVeigh, P., Kimber, M.J., Novozhilova, E. & Day, T.A. Neuropeptide signaling systems in flatworms. Parasitology 131, Suppl, S41–S55 (2005).
Brown, M.R. et al. Identification of a Drosophila brain-gut peptide related to the neuropeptide Y family. Peptides 20, 1035–1042 (1999).
Larhammar, D. Evolution of neuropeptide Y, peptide YY and pancreatic polypeptide. Regul. Pept. 62, 1–11 (1996).
Shen, P. & Cai, H.N. Drosophila neuropeptide F mediates integration of chemosensory stimulation and conditioning of the nervous system by food. J. Neurobiol. 47, 16–25 (2001).
Montell, C. Drosophila TRP channels. Pflugers Arch. 451, 19–28 (2005).
Montell, C., Birnbaumer, L. & Flockerzi, V. The TRP channels, a remarkably functional family. Cell 108, 595–598 (2002).
Moran, M.M., Xu, H. & Clapham, D.E. TRP ion channels in the nervous system. Curr. Opin. Neurobiol. 14, 362–369 (2004).
Ramsey, I.S., Delling, M. & Clapham, D.E. An introduction to TRP channels. Annu. Rev. Physiol. 68, 619–647 (2006).
Caterina, M.J. & Julius, D. The vanilloid receptor: a molecular gateway to the pain pathway. Annu. Rev. Neurosci. 24, 487–517 (2001).
Caterina, M.J. et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389, 816–824 (1997).
Tracey, W.D., Jr., Wilson, R.I., Laurent, G. & Benzer, S. painless, a Drosophila gene essential for nociception. Cell 113, 261–273 (2003).
Thomas, D. Predation on the soil inhabiting stages of the Mexican fruit fly. Southwest. Entomol. 20, 61–71 (1995).
Alyokhin, A., Mille, C., Messing, R. & Duan, J. Selection of pupation habitats by oriental fruit fly larvae in the laboratory. J. Insect Behav. 14, 57–67 (2001).
Kitamoto, T. Targeted expression of temperature-sensitive dynamin to study neural mechanisms of complex behavior in Drosophila. J. Neurogenet. 16, 205–228 (2002).
Marella, S. et al. Imaging taste responses in the fly brain reveals a functional map of taste category and behavior. Neuron 49, 285–295 (2006).
Tobin, D. et al. Combinatorial expression of TRPV channel proteins defines their sensory functions and subcellular localization in C. elegans neurons. Neuron 35, 307–318 (2002).
Cohen, B., Wimmer, E.A. & Cohen, S.M. Early development of leg and wing primordia in the Drosophila embryo. Mech. Dev. 33, 229–240 (1991).
Lakes-Harlan, R., Pollack, G.S. & Merritt, D.J. From embryo to adult: anatomy and development of a leg sensory organ in Phormia regina Meigen (Insecta: Diptera). I. Anatomy and physiology of a larval “leg” sensory organ. J. Comp. Neurol. 308, 188–199 (1991).
Liu, L., Yermolaieva, O., Johnson, W.A., Abboud, F.M. & Welsh, M.J. Identification and function of thermosensory neurons in Drosophila larvae. Nat. Neurosci. 6, 267–273 (2003).
Ji, R.R., Zhang, X., Wiesenfeld-Hallin, Z. & Hokfelt, T. Expression of neuropeptide Y and neuropeptide Y (Y1) receptor mRNA in rat spinal cord and dorsal root ganglia following peripheral tissue inflammation. J. Neurosci. 14, 6423–6434 (1994).
Al-Anzi, B., Tracey, W.D., Jr. & Benzer, S. Response of Drosophila to wasabi is mediated by painless, the fly homolog of mammalian TRPA1/ANKTM1. Curr. Biol. 16, 1034–1040 (2006).
Heilig, M. The NPY system in stress, anxiety and depression. Neuropeptides 38, 213–224 (2004).
Greco, B. & Carli, M. Reduced attention and increased impulsivity in mice lacking NPY Y2 receptors: relation to anxiolytic-like phenotype. Behav. Brain Res. 169, 325–334 (2006).
Tatemoto, K. Neuropeptide Y: history and overview. Handb. Exp. Pharmacol. 162, 1–21 (2004).
Li, J.-J., Zhou, X. & Yu, L.-C. Involvement of neuropeptide Y and Y1 receptor in antinociception in the arcuate nucleus of hypothalamus, an immunohistochemical and pharmacological study in intact rats and rats with inflammation. Pain 118, 232–242 (2005).
Naveilhan, P. et al. Reduced antinociception and plasma extravasation in mice lacking a neuropeptide Y receptor. Nature 409, 513–517 (2001).
Gibbs, J., Flores, C.M. & Hargreaves, K.M. Neuropeptide Y inhibits capsaicin-sensitive nociceptors via a Y1 receptor–mediated mechanism. Neuroscience 125, 703–709 (2004).
Roberts, D.B. Drosophila: A Practical Approach (IRL Press, Washington, D.C., 1986).
Wen, T., Parrish, C.A., Xu, D., Wu, Q. & Shen, P. Drosophila neuropeptide F and its receptor, NPFR1, define a signaling pathway that acutely modulates alcohol sensitivity. Proc. Natl. Acad. Sci. USA 102, 2141–2146 (2005).
Scott, K. et al. A chemosensory gene family encoding candidate gustatory and olfactory receptors in Drosophila. Cell 104, 661–673 (2001).
Macleod, G.T., Hegstrom-Wojtowicz, M., Charlton, M.P. & Atwood, H.L. Fast calcium signals in Drosophila motor neuron terminals. J. Neurophysiol. 88, 2659–2663 (2002).
Fan, X. et al. New statistical methods enhance imaging of cameleon fluorescence resonance energy transfer in cultured zebrafish spinal neurons. J. Biomed. Opt. 12, 034017 (2007).
Broder, J. et al. Estimating weak ratiometric signals in imaging data. I. Dual-channel data. J. Opt. Soc. Am. A Opt. Image Sci. Vis. 24, 2921–2931 (2007).
Thomson, D. Spectrum estimation and harmonic analysis. Proc. IEEE 70, 1055–1096 (1982).
Mitra, P.P. & Pesaran, B. Analysis of dynamic brain imaging data. Biophys. J. 76, 691–708 (1999).
Sornborger, A., Sailstad, C., Kaplan, E. & Sirovich, L. Spatiotemporal analysis of optical imaging data. Neuroimage 18, 610–621 (2003).
Mitra, P. & Bokil, H. Observed Brain Dynamics (Oxford University Press, New York, 2008).
Acknowledgements
The authors thank S. Benzer, W.D. Tracey, L. Liu, M. Welsch, K. Scott and H. Kitamoto for fly strains. This work is supported by grants from the US National Institutes of Health (AA014348 and DK058348 to P.S. and EB005432 to A.T.S.).
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J.X. carried out the behavioral and imaging experiments. J.K.L. contributed to the behavioral assays and immunostaining. A.T.S. supervised the design of the imaging experiments and data analysis. A.T.S. and J.X. performed imaging data analysis, and helped with writing the manuscript. P.S. supervised the project and wrote the manuscript.
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Xu, J., Sornborger, A., Lee, J. et al. Drosophila TRPA channel modulates sugar-stimulated neural excitation, avoidance and social response. Nat Neurosci 11, 676–682 (2008). https://doi.org/10.1038/nn.2119
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DOI: https://doi.org/10.1038/nn.2119
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