{
  "abstract": "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 Drosophila melanogaster , 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 OAα2R and mGluR receptors, providing transmitter-specific feedback. Postsynaptically, glutamate inhibits the approach-promoting MBON-11 neuron via GluClα 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.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "Antoine Prunier"
    },
    {
      "name": "Lewis M Sherer"
    },
    {
      "name": "Mariana da Silva"
    },
    {
      "name": "Samantha Chong"
    },
    {
      "name": "Léa Bihl"
    },
    {
      "name": "R. Steven Stowers"
    },
    {
      "name": "Sarah J Certel"
    },
    {
      "name": "Séverine Trannoy"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eg3grq0pq2j3d.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aec4153",
  "fulltext_url": null,
  "id": "eg3grq0pq2j3d",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://hal.science/hal-05760485v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.neu"
    ],
    [
      "openalex",
      "2804|Neurobiology and Insect Physiology Research"
    ]
  ],
  "openalex": "W7203495303",
  "pdf_url": "https://hal.science/hal-05760485/document",
  "pmcid": null,
  "pmid": "42600011",
  "published": "2026-08-14",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/eg3grq0pq2j3d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:39Z",
      "native_id": "hal-05760485",
      "source": "hal",
      "url": "https://hal.science/hal-05760485v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:1.sdv.neu",
      "subfield": "neuroscience"
    }
  ],
  "title": "An octopamine-glutamate cotransmitting neuron gates aggressive escalation through layered inhibition in Drosophila",
  "title_text": "An octopamine-glutamate cotransmitting neuron gates aggressive escalation through layered inhibition in Drosophila",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:39Z",
  "url": "https://research.draconitic.com/paper/eg3grq0pq2j3d",
  "venue": "Science Advances",
  "versions": []
}