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Social challenges like territorial intrusions evoke behavioral responses in widely diverging species. Recent work has showed that evolutionary "toolkits"-genes and modules with lineage-specific variations but deep conservation of function-participate in the behavioral response to social challenge. Here, we develop a multispecies computational-experimental approach to characterize such a toolkit at a systems level. Brain transcriptomic responses to social challenge was probed via RNA-seq profiling in three diverged species-honey bees, mice and three-spined stickleback fish-following a common methodology, allowing fair comparisons across species. Data were collected from multiple brain regions and multiple time points after social challenge exposure, achieving anatomical and temporal resolution substantially greater than previous work. We developed statistically rigorous analyses equipped to find homologous functional groups among these species at the levels of individual genes, functional and coexpressed gene modules, and transcription factor subnetworks. We identified six orthogroups involved in response to social challenge, including groups represented by mouse genes Npas4 and Nr4a1, as well as common modulation of systems such as transcriptional regulators, ion channels, G-protein-coupled receptors and synaptic proteins. We also identified conserved coexpression modules enriched for mitochondrial fatty acid metabolism and heat shock that constitute the shared neurogenomic response. Our analysis suggests a toolkit wherein nuclear receptors, interacting with chaperones, induce transcriptional changes in mitochondrial activity, neural cytoarchitecture and synaptic transmission after social challenge. It shows systems-level mechanisms that have been repeatedly co-opted during evolution of analogous behaviors, thus advancing the genetic toolkit concept beyond individual genes., (© 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

Social interactions can be divided into two categories, affiliative and agonistic. How neurogenomic responses reflect these opposing valences is a central question in the biological embedding of experience. To address this question, we exposed honey bees to a queen larva, which evokes nursing, an affiliative alloparenting interaction, and measured the transcriptomic response of the mushroom body brain region at different times after exposure. Hundreds of genes were differentially expressed at distinct time points, revealing a dynamic temporal patterning of the response. Comparing these results to our previously published research on agonistic aggressive interactions, we found both shared and unique transcriptomic responses to each interaction. The commonly responding gene set was enriched for nuclear receptor signaling, the set specific to nursing was enriched for olfaction and neuron differentiation, and the set enriched for aggression was enriched for cytoskeleton, metabolism, and chromosome organization. Whole brain histone profiling after the affiliative interaction revealed few changes in chromatin accessibility, suggesting that the transcriptomic changes derive from already accessible areas of the genome. Although only one stimulus of each type was studied, we suggest that elements of the observed transcriptomic responses reflect molecular encoding of stimulus valence, thus priming individuals for future encounters. This hypothesis is supported by behavioral analyses showing that bees responding to either the affiliative or agonistic stimulus exhibited a higher probability of repeating the same behavior but a lower probability of performing the opposite behavior. These findings add to our understanding of the biological embedding at the molecular level., (© 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

Understanding how social experiences are represented in the brain and shape future responses is a major challenge in the study of behavior. We addressed this problem by studying behavioral, transcriptomic and epigenetic responses to intrusion in honey bees. Previous research showed that initial exposure to an intruder provokes an immediate attack; we now show that this also leads to longer-term changes in behavior in the response to a second intruder, with increases in the probability of responding aggressively and the intensity of aggression lasting 2 and 1 h, respectively. Previous research also documented the whole-brain transcriptomic response; we now show that in the mushroom bodies (MBs) there are 2 waves of gene expression, the first highlighted by genes related to cytoskeleton remodeling, and the second highlighted by genes related to hormones, stress response and transcription factors (TFs). Overall, 16 of 37 (43%) of the TFs whose cis-motifs were enriched in the promoters of the differentially expressed genes (DEGs) were also predicted from transcriptional regulatory network analysis to regulate the MB transcriptional response, highlighting the strong role played by a relatively small subset of TFs in the MB's transcriptomic response to social challenge. Whole brain histone profiling showed few changes in chromatin accessibility in response to social challenge; most DEGs were 'ready' to be activated. These results show how biological embedding of a social challenge involves temporally dynamic changes in the neurogenomic state of a prominent region of the insect brain that are likely to influence future behavior., (© 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)