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Abstract Inhibitors of enzymes that inactivate amine neurotransmitters (dopamine, serotonin), such as catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), are thought to increase neurotransmitter levels and are widely used to treat Parkinson's disease and psychiatric disorders, yet the role of these enzymes in regulating behavior remains unclear. Here, we investigated the genetic loss of a similar enzyme in the model organismDrosophila melanogaster. Because the enzyme Ebony modifies and inactivates amine neurotransmitters, its loss is assumed to increase neurotransmitter levels, increasing behaviors such as aggression and courtship and decreasing sleep. Indeed,ebonymutants have been described since 1960 as aggressive mutants, though this behavior has not been quantified. Using automated machine learning-based analyses, we quantitatively confirmed thatebonymutants exhibited increased aggressive behaviors such as boxing but also decreased courtship behaviors and increased sleep. Through tissue-specific knockdown, we found thatebony’s role in these behaviors was specific to glia. Unexpectedly, direct measurement of amine neurotransmitters inebonybrains revealed that their levels were not increased but reduced. Thus, increased aggression is the anomalous behavior for this neurotransmitter profile. We further found thatebonymutants exhibited increased aggression only when fighting each other, not when fighting wild-type controls. Moreover, fights betweenebonymutants were less likely to end with a clear winner than fights between controls or fights betweenebonymutants and controls. Inebonyvs. control fights,ebonymutants were more likely to win. Together, these results suggest thatebonymutants exhibit prolonged aggressive behavior only in a specific context, with an equally dominant opponent.more » « less
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Mitra, Saheli; Chen, Mei-Tung; Stedman, Francisca; Hernandez, Jedidiah; Kumble, Grace; Kang, Xi; Zhang, Churan; Tang, Grace; Daugherty, Ian; Liu, Wanqing; et al (, The Journal of Physical Chemistry B)
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