Brain mitochondrial bioenergetics change with rapid and prolonged shifts in aggression in the honey bee, Apis mellifera

Abstract

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.

Biogenic amines and activity levels alter the neural energetic response to aggressive social cues in the honey bee Apis mellifera

“…In order to determine the relationship between biogenic amine signaling and neural energetic state with respect to aggression, we assess the brain mitochondrial response to alarm pheromone in a simple laboratory context. In doing so, we note a contradiction in the direction of the mitochondrial bioenergetics response compared to that observed in the field (Rittschof et al, ). We evaluate whether this disparity is a function of multimodal cue presence in the field versus lab, or a function of individual activity levels at the time of the assay.…”

“…The neural energetic state of neurons and glial cells, however, also alters signaling potential of neural circuits and responds to signaling events. Several studies have demonstrated that neural energetic state, described as the activity of metabolic pathways, including glycolysis and oxidative phosphorylation, predicts the outcome of social interactions (Hollis et al, ; van der Kooij et al, ; Li‐Byarlay, Rittschof, Massey, Pittendrigh, & Robinson, ; Rittschof, Vekaria, Palmer, & Sullivan, ), and is regulated by social experience (Alaux et al, ; Chandrasekaran et al, ; Dong et al, ; Li‐Byarlay et al, ; Rittschof et al, ). These studies observe such relationships at the whole brain level as well as in behavior‐relevant brain regions.…”

“…Honey bee aggression is socially modulated rapidly during an antipredator event, but it also shows stable individual variation as a function of age and developmental environment (Nouvian, Reinhard, & Giurfa, ; Rittschof, Coombs, Frazier, Grozinger, & Robinson, ; Rittschof & Hughes, ). Honey bee aggression is strongly associated with variation in neural energetics described using transcriptomic, metabolomics, and mitochondrial bioenergetics data (Chandrasekaran et al, ; Li‐Byarlay et al, ; Rittschof et al, , ; Rittschof, Coombs, et al, ; Rittschof & Hughes, ; Rittschof & Schirmeier, ). For example, we showed previously that both glycolysis and mitochondrial bioenergetics are rapidly (within 5 min) modulated in response to exposure to alarm pheromone (an aggression‐inducing olfactory social cue), applied in the natural colony context (Chandrasekaran et al, ; Rittschof et al, ).…”

“…Honey bee aggression is strongly associated with variation in neural energetics described using transcriptomic, metabolomics, and mitochondrial bioenergetics data (Chandrasekaran et al, ; Li‐Byarlay et al, ; Rittschof et al, , ; Rittschof, Coombs, et al, ; Rittschof & Hughes, ; Rittschof & Schirmeier, ). For example, we showed previously that both glycolysis and mitochondrial bioenergetics are rapidly (within 5 min) modulated in response to exposure to alarm pheromone (an aggression‐inducing olfactory social cue), applied in the natural colony context (Chandrasekaran et al, ; Rittschof et al, ). Furthermore, older bees, which are more behaviorally responsive to alarm pheromone (Breed, Robinson, & Page, ), have higher brain mitochondrial respiration rates compared to younger, more docile individuals.…”

“…Furthermore, older bees, which are more behaviorally responsive to alarm pheromone (Breed, Robinson, & Page, ), have higher brain mitochondrial respiration rates compared to younger, more docile individuals. Older bees also show greater plasticity in mitochondrial function in response to variation in metabolic substrates (Rittschof et al, ).…”