Socially responsive effects of brain oxidative metabolism on aggression

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 34; pp. 12533 - 12537
• Main Authors: Li-Byarlay, Hongmei, Rittschof, Clare C., Massey, Jonathan H., Pittendrigh, Barry R., Robinson, Gene E.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 26.08.2014; National Acad Sciences
• Subjects: adenosine triphosphate; aerobiosis; aggression; Aggression - drug effects; Aggression - physiology; Animals; Animals, Genetically Modified; Apis mellifera; Bees - drug effects; Bees - genetics; Bees - physiology; Behavior, Animal - drug effects; Behavior, Animal - physiology; Behavioral neuroscience; Benzoates - pharmacology; Biological Sciences; Brain; Brain - drug effects; Brain - physiology; cognition; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila melanogaster - physiology; Energy metabolism; fruit flies; gene expression; Gene Knockdown Techniques; Genes, Insect; genetic engineering; genetically modified organisms; glucose; Glucose - metabolism; Glycolysis; Honey; Honey bees; Human aggression; Hydrocarbons, Chlorinated - pharmacology; Insect behavior; Insect colonies; Insect genetics; Metabolism; Neurons; Neurons - metabolism; oxidation; oxidative phosphorylation; Oxidative Phosphorylation - drug effects; Oxygen; Phosphorylation; Plasticity; Pyrazoles - pharmacology; RNA interference; Social Behavior; Social Environment; transcriptomics; Ndufs7b; ND20-like; behavioral genomics; Warburg effect
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1412306111

Despite ongoing high energetic demands, brains do not always use glucose and oxygen in a ratio that produces maximal ATP through oxidative phosphorylation. In some cases glucose consumption exceeds oxygen use despite adequate oxygen availability, a phenomenon known as aerobic glycolysis. Although metabolic plasticity seems essential for normal cognition, studying its functional significance has been challenging because few experimental systems link brain metabolic patterns to distinct behavioral states. Our recent transcriptomic analysis established a correlation between aggression and decreased whole-brain oxidative phosphorylation activity in the honey bee (Apis mellifera), suggesting that brain metabolic plasticity may modulate this naturally occurring behavior. Here we demonstrate that the relationship between brain metabolism and aggression is causal, conserved over evolutionary time, cell type-specific, and modulated by the social environment. Pharmacologically treating honey bees to inhibit complexes I or V in the oxidative phosphorylation pathway resulted in increased aggression. In addition, transgenic RNAi lines and genetic manipulation to knock down gene expression in complex I in fruit fly (Drosophila melanogaster) neurons resulted in increased aggression, but knockdown in glia had no effect. Finally, honey bee colony-level social manipulations that decrease individual aggression attenuated the effects of oxidative phosphorylation inhibition on aggression, demonstrating a specific effect of the social environment on brain function. Because decreased neuronal oxidative phosphorylation is usually associated with brain disease, these findings provide a powerful context for understanding brain metabolic plasticity and naturally occurring behavioral plasticity.