@article{bc31c42c38ee4f168156a3f921cfe9d6,
title = "A neuropeptidergic circuit gates selective escape behavior of Drosophila larvae",
abstract = "Animals display selective escape behaviors when faced with environmental threats. Selection of the appropriate response by the underlying neuronal network is key to maximizing chances of survival, yet the underlying network mechanisms are so far not fully understood. Using synapse-level reconstruction of the Drosophila larval network paired with physiological and behavioral readouts, we uncovered a circuit that gates selective escape behavior for noxious light through acute and input-specific neuropeptide action. Sensory neurons required for avoidance of noxious light and escape in response to harsh touch, each converge on discrete domains of neuromodulatory hub neurons. We show that acute release of hub neuron-derived insulin-like peptide 7 (Ilp7) and cognate relaxin family receptor (Lgr4) signaling in downstream neurons are required for noxious light avoidance, but not harsh touch responses. Our work highlights a role for compartmentalized circuit organization and neuropeptide release from regulatory hubs, acting as central circuit elements gating escape responses.",
keywords = "connectomics, Drosophila melanogaster, escape behavior, GPCR, light avoidance, neuromodulation, neuropeptide, nociception, noxious light, sensory gating",
author = "Imambocus, {Bibi Nusreen} and Fangmin Zhou and Andrey Formozov and Annika Wittich and Tenedini, {Federico M.} and Chun Hu and Kathrin Sauter and {Mascarenhas Varela}, Ednilson and Fabiana Her{\'e}dia and Casimiro, {Andreia P.} and Andr{\'e} Macedo and Philipp Schlegel and Yang, {Chung Hui} and Irene Miguel-Aliaga and Wiegert, {J. Simon} and Pankratz, {Michael J.} and Gontijo, {Alisson M.} and Albert Cardona and Peter Soba",
note = "Funding Information: We would like to thank M. Petersen and A.R.M. Dias for excellent technical assistance; C. Wegener, T. Oertner, F. Morellini, J. Parrish, and Q. Yuan for comments on the manuscript; B. Ye, B. Hofbauer, and C. Wegener for communicating results prepublication; P. Herrero, C. Wegener, M. Wernet, and D. Anderson for fly stocks; T. Kazimier for advice and troubleshooting with CATMAID; and L. Herren for supervising Dp7 connectome reconstruction. P. Soba, B.N.I. and A.C. thank the visiting scientist program at HHMI Janelia, and HHMI Janelia for funding. Stocks obtained from the Bloomington Drosophila Stock Center (NIH grant P40OD018537) and Vienna Drosophila Resource Center (VDRC; http://stockcenter.vdrc.at) were used in this study. cDNA and cells obtained from the Drosophila Genomics Resource Center (NIH grant 2P40OD010949) were used in this study. This work was supported by the Deutsche Forschungsgemeinschaft (DFG; SO1337/4-1, SO1337/2-1/2-2, and SO1337/ 7-1 to P. Soba; WI4485/2-2 and WI4485/3-2 to J.S.W.), the DFG Heisenberg program (SO1337/6-1 to P. Soba), an Alexander von Humboldt Research Fellowship (to A.F.), an EMBO Short-Term Fellowship (to E.M.V.), the European Commission FP7 (PCIG13-GA-2013-618847 to A.M.G.), the European Research Council Horizon 2020 (ERC2016-StG-714762 to J.S.W.), the FCT (IF/00022/2012; Congento LISBOA-01-0145-FEDER-022170, co-financed by FCT/Lisboa2020; UID/Multi/04462/2019, PTDC/BEXBCM/1370/2014, and PTDC/BIA-BID/31071/2017 to A.M.G.; PTDC/MED-NEU/30753/2017 to F.H. and A.M.G.; and SFRH/BPD/94112/2013 to A.M.), PD/BD/52421/2013 to F.H. and SFRH/BD/135263/2017 via PGCD (Programa P?s-Gradua??o Ci?ncia Para o Desenvolvimento) to E.M.V. B.N.I. performed and analyzed most of the experiments, including connectome reconstruction and analysis, phototoxicity assays, light-avoidance behavior analysis, calcium imaging, and morphological analysis, and wrote the manuscript. A.W and F.Z. performed a subset of the light-avoidance assays. F.Z. and A.F. performed the locomotion and chemotaxis assays and analysis. A.F. wrote the custom analysis scripts and code. C.H. performed and analyzed experiments in semi-intact larval preparations. F.M.T. performed and analyzed the mechanonociceptive and optogenetic behavior assays. K.S. made the reagents and performed the co-immunoprecipitation experiments. E.M.V. performed and analyzed the pupariation assays. E.M.V. A.P.C. A.M. F.H. and A.M.G. developed Lgr4 transgenes and performed qPCR assays. P. Schlegel and M.J.P. performed the connectome reconstruction and analyses. C.-H.Y. and I.M.-A. developed the critical reagents. J.S.W. contributed to and supervised the behavioral analyses and custom code. A.C. performed and supervised the connectome reconstruction. P. Soba made the reagents, contributed to the circuit and behavioral analyses, supervised the work, and wrote the manuscript. The authors declare no competing interests. Funding Information: We would like to thank M. Petersen and A.R.M. Dias for excellent technical assistance; C. Wegener, T. Oertner, F. Morellini, J. Parrish, and Q. Yuan for comments on the manuscript; B. Ye, B. Hofbauer, and C. Wegener for communicating results prepublication; P. Herrero, C. Wegener, M. Wernet, and D. Anderson for fly stocks; T. Kazimier for advice and troubleshooting with CATMAID; and L. Herren for supervising Dp7 connectome reconstruction. P. Soba, B.N.I., and A.C. thank the visiting scientist program at HHMI Janelia, and HHMI Janelia for funding. Stocks obtained from the Bloomington Drosophila Stock Center ( NIH grant P40OD018537 ) and Vienna Drosophila Resource Center (VDRC; http://stockcenter.vdrc.at ) were used in this study. cDNA and cells obtained from the Drosophila Genomics Resource Center ( NIH grant 2P40OD010949 ) were used in this study. This work was supported by the Deutsche Forschungsgemeinschaft (DFG; SO1337/4-1 , SO1337/2-1/2-2 , and SO1337/ 7-1 to P. Soba; WI4485/2-2 and WI4485/3-2 to J.S.W.), the DFG Heisenberg program ( SO1337/6-1 to P. Soba), an Alexander von Humboldt Research Fellowship (to A.F.), an EMBO Short-Term Fellowship (to E.M.V.), the European Commission FP7 ( PCIG13-GA-2013-618847 to A.M.G.), the European Research Council Horizon 2020 ( ERC2016-StG-714762 to J.S.W.), the FCT ( IF/00022/2012 ; Congento LISBOA-01-0145-FEDER-022170 , co-financed by FCT/Lisboa2020 ; UID/Multi/04462/2019 , PTDC/BEXBCM/1370/2014 , and PTDC/BIA-BID/31071/2017 to A.M.G.; PTDC/MED-NEU/30753/2017 to F.H. and A.M.G.; and SFRH/BPD/94112/2013 to A.M.), PD/BD/52421/2013 to F.H., and SFRH/BD/135263/2017 via PGCD ( Programa P{\'o}s-Gradua{\c c}{\~a}o Ci{\^e}ncia Para o Desenvolvimento ) to E.M.V. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2022",
month = jan,
day = "10",
doi = "10.1016/j.cub.2021.10.069",
language = "English",
volume = "32",
pages = "149 -- 163.e8",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "1",
}