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Ruff, B.

Publications and source records attributed to Ruff, B..

3 recordsLinked to original sources

Neural circuits regulating social dominance implement a strategy predicted by evolutionary game theory

Social conflict is a fundamental challenge for all animals and determines access to critical resources like mates and food. Evolutionary game theory predicts that natural selection should yield competitive strategies that balance the benefits and costs of social conflict. However, whether such strategies are embedded within the neural circuits that regulate aggression remains unclear. Here, we identify a neural circuit regulating the decision to flee during fighting in male Drosophila and show that the onset of defeat is governed by a probabilistic strategy predicted by evolutionary game theory. This mechanism arises from the inhibition of Tk-GAL4FruM neurons that promote aggressive arousal in males. Inhibition is mediated by a mushroom body circuit involving PPL1 dopaminergic neurons and V2 mushroom body output neurons, both classically associated with aversive learning. Silencing this circuit disrupts the onset of defeat, while activating it induces rapid defeat. Conversely, activation of reward-encoding PAM dopaminergic neurons promotes winning, revealing a dual role for dopamine in shaping contest dynamics. Finally, we find that internal state variables such as hunger and motivation shift the defeat onset probability distribution, consistent with game theory predictions of how payoff modulates fighting persistence. Together, our results provide direct evidence that evolutionary strategies based on payoff, long described by game theory, are implemented as circuit-level computations that regulate aggression.

neuroscience↗

Cellular and functional dissection of the octopaminergic system in the Drosophila brain

Octopamine (OA) is a major biogenic amine in the invertebrate nervous system and is often considered a functional analog of vertebrate noradrenaline. Along with its immediate precursor tyramine (TA), OA influences diverse physiological and behavioral processes, including sensory processing and social behavior. However, understanding the neural basis of its multifunctionality has been constrained by the limited genetic access to defined OA/TA neuron types. Here, we present a curated set of transgenic driver strains that provide selective access to nearly all long-range OA/TA cell types in the brain of common fruit flies, Drosophila melanogaster. Using these tools, we map cell-type-specific innervation patterns, compare male and female neuroanatomy, and cross-reference identified neuron types with electron microscopy connectome datasets. As a proof of principle, we show that distinct optic lobe-projecting OA/TA neuron types differentially modulate visually guided behaviors, and we identify a novel OA/TA cell type that suppresses aggression in both sexes. This resource establishes a practical and conceptual foundation for cell-type-resolved analysis of OA/TA circuit function and enables direct integration of genetics, anatomy, and connectomics for studies of neuromodulatory circuit organization.

neuroscience↗

The homeobox transcription factor Cux1 coordinates postnatal epithelial developmental timing but is dispensable for lung organogenesis and regeneration

Lung epithelial progenitors use a complex network of known and predicted transcriptional regulators to influence early lung development. Here, we evaluate the function of one predicted regulator, Cux1, that we identified from transcriptional regulatory analysis of the SOX9+ distal lung progenitor network. We generated a new Cux1-floxed mouse model and created an epithelial-specific knockout of Cux1 using Shh-Cre (Cux1ShhCre-LOF). Postnatal Cux1ShhCre-LOF animals recapitulate key skin phenotypic features found in prior constitutive Cux1 knockout animals, confirming functionality of the new floxed model. Postnatal Cux1ShhCre-LOF mice displayed subtle alveolar simplification and a transient delay in alveologenesis without persistent lung phenotypes or alterations in lung epithelial cell allocation. Cux1ShhCre-LOF mice developed failure to thrive in their second and third weeks of life due to delayed ileal maturation, which similarly resolves by postnatal day 35. Finally, we challenged Cux1ShhCre-LOF with influenza-mediated lung injury to demonstrate that Cux1ShhCre-LOF mice undergo productive alveolar regeneration that is indistinguishable from WT animals. Together, these findings indicate that epithelial-specific loss of Cux1 leads to transient developmental delays in the skin, lung, and intestine without defects in definitive organogenesis. One-Sentence SummaryDeletion of key DNA binding domains leads to loss of Cux1 function in the lung, intestine, and skin characterized by transient failure to thrive without significant adult disease.

developmental biology↗