Authors
Antoine Prunier, Lewis M Sherer, Mariana Da Silva, Samantha Chong, Léa Bihl, R Steven Stowers, Sarah J Certel, Séverine Trannoy
Published in
Science advances. Volume 12. Issue 33. Pages eaec4153. Aug 14, 2026. Epub Aug 14, 2026.
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.
PMID:
42600011
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.
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