Neuronal function demands high-level energy production, and as such, a decline in mitochondrial respiration characterizes brain injury and disease. A growing number of studies, however, link brain mitochondrial function to behavioral modulation in non-diseased contexts. In the honey bee, we show for the first time that an acute social interaction, which invokes an aggressive response, may also cause a rapid decline in brain mitochondrial bioenergetics. The degree and speed of this decline has only been previously observed in the context of brain injury. Furthermore, in the honey bee, age-related increases in aggressive tendency are associated with increased baseline brain mitochondrial respiration, as well as increased plasticity in response to metabolic fuel type Similarly, diet restriction and ketone body feeding, which commonly enhance mammalian brain mitochondrial function, cause increased aggression. Thus, even in normal behavioral contexts, brain mitochondria show a surprising degree of variation in function over both rapid and prolonged time scales, with age predicting both baseline function and plasticity in function. These results suggest that mitochondrial function is integral to modulating aggression-related neuronal signaling. We hypothesize that variation in function reflects mitochondrial calcium buffering activity, and that shifts in mitochondrial function signal to the neuronal soma to regulate gene expression and neural energetic state. Modulating brain energetic state is emerging as a critical component of the regulation of behavior in non-diseased contexts.

Mitochondrial activity is highly dynamic in the healthy brain, and it can reflect both the signaling potential and the signaling history of neural circuits. Recent studies spanning invertebrates to mammals have highlighted a role for neural mitochondrial dynamics in learning and memory processes as well as behavior. In the current study, we investigate the interplay between biogenic amine signaling and neural energetics in the honey bee, Apis mellifera. In this species, aggressive behaviors are regulated by neural energetic state and biogenic amine titers, but it is unclear how these mechanisms are linked to impact behavioral expression. We show that brain mitochondrial number is highest in aggression‐relevant brain regions and in individual bees that are most responsive to aggressive cues, emphasizing the importance of energetics in modulating this phenotype. We also show that the neural energetic response to alarm pheromone, an aggression inducing social cue, is activity dependent, modulated by the “fight or flight” insect neurotransmitter octopamine. Two other neuroactive compounds known to cause variation in aggression, dopamine, and serotonin, also modulate neural energetic state in aggression‐relevant regions of the brain. However, the effects of these compounds on respiration at baseline and following alarm pheromone exposure are distinct, suggesting unique mechanisms underlying variation in mitochondrial respiration in these circuits. These results motivate new explanations for the ways in which biogenic amines alter sensory perception in the context of aggression. Considering neural energetics improves predictions about the regulation of complex and context‐dependent behavioral phenotypes.

Maternal stress is a common source of heritable health and behavioral variation. This type of maternal effect could be particularly important for honey bees (Apis mellifera), as a single queen is responsible for many generations of workers who perform all colony functions including raising subsequent worker generations. Multiple factors work synergistically to cause colony loss, but a role for maternal stress effects is unstudied. We used an artificial cold temperature treatment as a proof-of-concept approach to investigate whether acute queen stress causes changes in worker phenotypes, including egg hatching rate, development time, and adult behavior and immune function. We found that queen stress impacts early-life phenotypes (egg hatching and development time), with more limited impacts on adult phenotypes (behavior and immune function). Thus, if maternal stress impacts colony health, it is likely through cumulative impacts on worker population numbers, not through phenotypic effects that impact individual adult worker behavior or health resilience. This study addresses an important and overlooked question, and provides a baseline understanding of the likely impacts of queen stress on worker phenotypes.

Gene expression changes resulting from social interactions may give rise to long term behavioral change, or simply reflect the activity of neural circuitry associated with behavioral expression. In honey bees, social cues broadly modulate aggressive behavior and brain gene expression. Previous studies suggest that expression changes are limited to contexts in which social cues give rise to stable, relatively long-term changes in behavior. Here we use a traditional beekeeping approach that inhibits aggression, smoke exposure, to deprive individuals of aggression-inducing olfactory cues and evaluate whether behavioral changes occur in absence of expression variation in a set of four biomarker genes (drat, cyp6g1/2, GB53860, inos) associated with aggression in previous studies. We also evaluate two markers of a brain hypoxic response (hif1α, hsf) to determine whether smoke induces molecular changes at all. We find that bees with blocked sensory perception as a result of smoke exposure show a strong, temporary inhibition of aggression relative to bees allowed to perceive normal social cues. However, blocking sensory perception had minimal impacts on aggression-relevant gene expression, althought it did induce a hypoxic molecular response in the brain. Results suggest that certain genes differentiate social cue-induced changes in aggression from long-term modulation of this phenotype.