{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T18:35:46Z","timestamp":1786732546266,"version":"build-2736575974"},"reference-count":79,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"33","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2R01GM115510"],"award-info":[{"award-number":["2R01GM115510"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2R01GM115510"],"award-info":[{"award-number":["2R01GM115510"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-19-CE37-0018-01"],"award-info":[{"award-number":["ANR-19-CE37-0018-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-25-CE37-7191-01"],"award-info":[{"award-number":["ANR-25-CE37-7191-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003135","name":"Fondation Fyssen","doi-asserted-by":"publisher","award":["190573"],"award-info":[{"award-number":["190573"]}],"id":[{"id":"10.13039\/501100003135","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:p>\n                    Aggression is an evolutionarily conserved behavior essential for survival and reproduction, yet escalation to high-intensity forms entails substantial metabolic costs and injury risks, necessitating precise neural control. Using\n                    <jats:italic toggle=\"yes\">Drosophila melanogaster<\/jats:italic>\n                    , we uncovered a multilayered inhibitory circuit that constrains aggressive escalation. This circuit involves a cotransmitting octopamine-glutamate ventral paired medial 4 (VPM4) neuron and its downstream GABAergic target, MBON-11. Neurotransmitter-specific manipulations reveal that octopamine and glutamate release from VPM4 is independently regulated by presynaptic OA\u03b12R and mGluR receptors, providing transmitter-specific feedback. Postsynaptically, glutamate inhibits the approach-promoting MBON-11 neuron via GluCl\u03b1 receptors, restraining transitions to high-intensity aggression and supporting a role in approach\/avoidance behaviors. Furthermore, the Rdl GABAergic receptor within MBON-11 neurons provides rapid inhibitory feedback, creating an additional layer of regulation. Together, these findings reveal a circuit architecture in which cotransmission and inhibitory feedback loops form a layered inhibition mechanism that continuously constrains escalation, indicating that aggression intensity is actively regulated to align behavior with context and cost-benefit trade-offs.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aec4153","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T17:58:41Z","timestamp":1786730321000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["An octopamine-glutamate cotransmitting neuron gates aggressive escalation through layered inhibition in\n                    <i>Drosophila<\/i>"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1137-0115","authenticated-orcid":true,"given":"Antoine","family":"Prunier","sequence":"first","affiliation":[{"name":"Research Center for Animal Cognition, Integrative Biology Center, Toulouse University, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5875-1737","authenticated-orcid":true,"given":"Lewis M.","family":"Sherer","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Brown University, Providence, RI, USA."},{"name":"Division of Biological Science, Neuroscience Program, University of Montana, Missoula, MT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2780-5895","authenticated-orcid":true,"given":"Mariana","family":"Da Silva","sequence":"additional","affiliation":[{"name":"Research Center for Animal Cognition, Integrative Biology Center, Toulouse University, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4833-2914","authenticated-orcid":true,"given":"Samantha","family":"Chong","sequence":"additional","affiliation":[{"name":"Barnard College, New York City, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a","family":"Bihl","sequence":"additional","affiliation":[{"name":"Research Center for Animal Cognition, Integrative Biology Center, Toulouse University, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1473-2478","authenticated-orcid":true,"given":"R. Steven","family":"Stowers","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, Montana State University, Bozeman, MT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2039-2657","authenticated-orcid":true,"given":"Sarah J.","family":"Certel","sequence":"additional","affiliation":[{"name":"Division of Biological Science, Neuroscience Program, University of Montana, Missoula, MT, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5059-9846","authenticated-orcid":true,"given":"S\u00e9verine","family":"Trannoy","sequence":"additional","affiliation":[{"name":"Research Center for Animal Cognition, Integrative Biology Center, Toulouse University, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"K. Lorenz On Aggression (Harcourt Brace and World 1963)."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cobeha.2016.08.005"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1017\/S146479310500686X"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00715-2"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0196954"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-072116-031240"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-024-03936-0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2014.04.010"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2969"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008609"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.56"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.082102599"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404693101"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/254511a0"},{"key":"e_1_3_2_16_2","first-page":"RP107559","article-title":"Aggressive trait selection influences life-history trade-offs, favoring survival over reproductive success in Drosophila melanogaster males","volume":"14","author":"Defert A.","year":"2025","unstructured":"A. Defert, R. Gout, G. Pennot, F. Jamme, A. Castex, A. Handjar, T. Guilleman, J. C. Billeter, S. Trannoy, Aggressive trait selection influences life-history trade-offs, favoring survival over reproductive success in Drosophila melanogaster males. eLife 14, RP107559 (2025).","journal-title":"eLife"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.04577"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0198362"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.07.028"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.12.023"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.04.034"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.04.040"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.04580"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105626"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07558-y"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07001"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.top107985"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-19-07297.2000"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.06.021"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2018.00113"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2017.09.010"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(99)00032-7"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.108225"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2007.12.052"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013248"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004356"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2164"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6517-11.2012"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.03.015"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1117689109"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/g3journal\/jkae012"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2003.07.019"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700328104"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-19-07503.1997"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1737042100"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e3282f524c7"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1046-5928(03)00100-1"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2025.05.024"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1888-9891(09)72404-8"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1074"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.11.019"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature21716"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2015.10.002"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsbl.2019.0084"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1716612115"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1901292116"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1101\/lm.053918.124"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.49257"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128101"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.12.014"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2413134122"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cois.2024.101293"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-010-1920-x"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-008-9600-5"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2022.109540"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12872"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06864"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.57443"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0694-14.2014"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1176-21.2021"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220560110"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0432-23.2023"},{"key":"e_1_3_2_73_2","doi-asserted-by":"crossref","unstructured":"Z. Vahdat O. Gambrell A. Singh Characterizing the role of autaptic feedback in enhancing precision of neuronal firing times. bioRxiv 561207 (2023).","DOI":"10.1101\/2023.10.06.561207"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.58942"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2010.07.045"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot108144"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1111\/2041-210X.12584"},{"key":"e_1_3_2_78_2","doi-asserted-by":"crossref","unstructured":"E. Eyjolfsdottir S. Branson X. P. Burgos-Artizzu E. D. Hoopfer J. Schor D. J. Anderson P. Perona \u201cDetecting social actions of fruit flies \u201d in Computer Vision \u2013 ECCV 2014 (Springer International Publishing Cham 2014) pp. 772\u2013787.","DOI":"10.1007\/978-3-319-10605-2_50"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2281"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3567"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aec4153","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T17:59:48Z","timestamp":1786730388000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aec4153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":79,"journal-issue":{"issue":"33","published-print":{"date-parts":[[2026,8,14]]}},"alternative-id":["10.1126\/sciadv.aec4153"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aec4153","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]},"assertion":[{"value":"2025-09-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaec4153"}}