An octopamine-glutamate cotransmitting neuron gates aggressive escalation through layered inhibition in Drosophila
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.
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BibTeX
@article{prunier2026octopamineglutamate,
title = {{An octopamine-glutamate cotransmitting neuron gates aggressive escalation through layered inhibition in Drosophila}},
author = {Antoine Prunier and Lewis M Sherer and Mariana da Silva and Samantha Chong and Léa Bihl and R. Steven Stowers and Sarah J Certel and Séverine Trannoy},
journal = {Science Advances},
year = {2026},
month = aug,
doi = {10.1126/sciadv.aec4153},
url = {https://hal.science/hal-05760485v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - An octopamine-glutamate cotransmitting neuron gates aggressive escalation through layered inhibition in Drosophila
AU - Antoine Prunier
AU - Lewis M Sherer
AU - Mariana da Silva
AU - Samantha Chong
AU - Léa Bihl
AU - R. Steven Stowers
AU - Sarah J Certel
AU - Séverine Trannoy
PY - 2026
DA - 2026/08/14
JO - Science Advances
DO - 10.1126/sciadv.aec4153
UR - https://hal.science/hal-05760485v1
AB - 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.
SN - 2375-2548
ER -