Temporal dynamics of neurogenomic plasticity in response to social interactions in male threespined sticklebacks

Abstract

Animals exhibit dramatic immediate behavioral plasticity in response to social interactions, and brief social interactions can shape the future social landscape. However, the molecular mechanisms contributing to behavioral plasticity are unclear. Here, we show that the genome dynamically responds to social interactions with multiple waves of transcription associated with distinct molecular functions in the brain of male threespined sticklebacks, a species famous for its behavioral repertoire and evolution. Some biological functions (e.g., hormone activity) peaked soon after a brief territorial challenge and then declined, while others (e.g., immune response) peaked hours afterwards. We identify transcription factors that are predicted to coordinate waves of transcription associated with different components of behavioral plasticity. Next, using H3K27Ac as a marker of chromatin accessibility, we show that a brief territorial intrusion was sufficient to cause rapid and dramatic changes in the epigenome. Finally, we integrate the time course brain gene expression data with a transcriptional regulatory network, and link gene expression to changes in chromatin accessibility. This study reveals rapid and dramatic epigenomic plasticity in response to a brief, highly consequential social interaction.

Deep evolutionary conservation of autism-related genes

“…However, this type of information is particularly important to our understanding of the relationship between animal behaviors and human mental health disorders. Emerging evidence for conserved molecular mechanisms for social behaviors between invertebrates and vertebrates (9)(10)(11)(12)(13)(14) suggests that there are similar connections to mental health disorders.…”

Cross‐species systems analysis of evolutionary toolkits of neurogenomic response to social challenge

“…While measurements approximately 30 minutes after stimulus exposure were used in previous work, the addition of 60 and 120 minutes allows us to more broadly accommodate the cross‐species variations in the timing of transcriptional trajectory; such variations may arise from differences in molecular mechanisms and may also reflect differences in animal behavior such as the time it takes to recover from a social challenge. For details about the specific experimental paradigms used within each individual species, see our previous work …”

“…The experimental design integrated datasets on mice, sticklebacks and honey bees. Insights into the social neural transcriptomes for each of these individual species have been published . These datasets were sequenced in parallel, allowing for comparative analysis and discovery of shared mechanisms with minimal technical variation.…”

“…Such a design cannot capture longer‐acting genetic programs. This simple design also limits the power of this previous study to detect responses whose anatomical and temporal profiles are shaped by the unique cell biology, neuroendocrine and metabolic properties of brains in these three species …”

“…We report here the results of a detailed computational investigation of the shared molecular roots of social behavior, specifically neural response to social challenge, that remedies the above issues. We utilized a powerful analytical design, integrating for the first time three previously published large time series datasets of brain gene expression from mice, three‐spined sticklebacks and honey bees . To interrogate these datasets at a systems‐level, we developed a suite of computational methods that allowed us to ascertain not only individual genes, but also to overcome complex orthology and incomplete annotations in order to identify coordinately expressed gene ontology (GO) terms, coexpression networks and transcriptional regulatory cascades commonly associated with a behaviorally relevant stimulus across these distantly related species.…”