An octopamine-glutamate cotransmitting neuron gates aggressive escalation through layered inhibition in <i>Drosophila</i>.

Overview

1. Research Center for Animal Cognition, Integrative Biology Center, Toulouse University, Toulouse, France
2. Department of Neuroscience, Brown University, Providence, RI, USA
3. Division of Biological Science, Neuroscience Program, University of Montana, Missoula, MT, USA
4. Barnard College, New York City, NY, USA
5. Department of Microbiology & Immunology, Montana State University, Bozeman, MT, USA

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.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

• zenodo:18662708, at Zenodo; found in “Data, code, and materials availability:”
• zenodo:18662981, at Zenodo; found in “Data, code, and materials availability:”
• zenodo:18685975, at Zenodo; found in “Data, code, and materials availability:”
• zenodo:18704606, at Zenodo; found in “Data, code, and materials availability:”
• zenodo:18717039, at Zenodo; found in “Data, code, and materials availability:”
• zenodo:21239060, at Zenodo; found in “Data, code, and materials availability:”

Data, code, and materials availability

All data and code needed to evaluate and reproduce the results in the paper are present in the paper and/or the Supplemental Materials. This study generates new fly lines that will be made available upon request to the corresponding authors. Videos and materials used during the study are available via Zenodo links: Fig. 1 (D to J): https://doi.org/10.5281/zenodo.18662708; Fig. 1 (K and L): https://doi.org/10.5281/zenodo.18662981; Fig. 2 (C to E and J): https://doi.org/10.5281/zenodo.18704606; Fig. 2 (F to I): https://doi.org/10.5281/zenodo.18717039; Fig. 3 (B to D): https://doi.org/10.5281/zenodo.18685975; Fig. 4 (C to F): https://doi.org/10.5281/zenodo.21239060; Fig. 5 (A to C): https://doi.org/10.5281/zenodo.21245441; Fig. 5 (D to F): https://doi.org/10.5281/zenodo.21245523; Fig. 6 (B to D): https://doi.org/10.5281/zenodo.21246850; Fig. 6 (E to G): https://doi.org/10.5281/zenodo.21246853; Fig. 7 (A to D): https://doi.org/10.5281/zenodo.21245655; fig. S1: https://doi.org/10.5281/zenodo.18670398; fig. S2: https://doi.org/10.5281/zenodo.18746277; fig. S3: https://doi.org/10.5281/zenodo.18663169; fig. S4: https://doi.org/10.5281/zenodo.18669428; fig. S5: https://doi.org/10.5281/zenodo.18670306; fig. S6: https://doi.org/10.5281/zenodo.18670514.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 10 MeSH terms, 3 funders, 73 references.

Cite

This paper

Prunier, A., Sherer, L. M., Da Silva, M., Chong, S., Bihl, L., Stowers, R. S., Certel, S. J., & Trannoy, S. (2026). An octopamine-glutamate cotransmitting neuron gates aggressive escalation through layered inhibition in <i>Drosophila</i>. Science advances, 12(33), eaec4153. https://doi.org/10.1126/sciadv.aec4153

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1016/j.isci.2026.115564 [code]

Octopamine regulates neural circuits in the mushroom body and central complex, influencing sleep and arousal.

Journal: iScience

In common: 9 references

[2] doi:10.1038/s41586-026-10735-w [code]

Distributed control circuits across a brain-and-cord connectome.

Journal: Nature

In common: drosophila, 8 references

[3] doi:10.3389/fnsys.2026.1822122 [code]

Convergence-divergence circuits for multimodal integration of innate and learned opponent valences.

Journal: Frontiers in systems neuroscience

In common: 8 references

[4] doi:10.1038/s41593-026-02381-2 [code]

Creating true and false memories from forgotten information in Drosophila.

Journal: Nature neuroscience

In common: drosophila, 4 references

[5] doi:10.1038/s41586-026-10797-w [code]

A global molecular code for birth order and neuronal identity in Drosophila.

Journal: Nature

In common: drosophila, cellular / molecular, 3 references

[6] doi:10.1038/s41467-026-72057-9 [code]

Sex-specific behavioral feedback modulates sensorimotor processing and drives flexible social behavior.

Journal: Nature communications

In common: drosophila, 3 references

[7] doi:10.7554/elife.96084 [code]

Organization of circuits linking descending input to motor output in the <i>Drosophila</i> Male Adult Nerve Cord connectome.

Journal: eLife

In common: drosophila, 3 references

[8] doi:10.7554/elife.108675 [code]

SynaptoTagMe, a toolkit for in vivo mapping and modulating neurotransmission at single-cell resolution.

Journal: eLife

In common: cellular / molecular, 3 references

[9] doi:10.1038/s41467-026-72152-x [code]

Centralized brain networks controlling antennal grooming coordination.

Journal: Nature communications

In common: drosophila, 3 references

[10] doi:10.1371/journal.pgen.1011985

Social isolation upregulates takeout expression in female Drosophila melanogaster to promote sucrose preference.

Journal: PLoS genetics

In common: drosophila, cellular / molecular, 2 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.