Troy, J. M. | bioRxiv Science

bioRxiv2021

An epigenomic shift in amygdala marks the transition from pup-aversive to maternal-like behaviors in alloparenting virgin female mice

In many species, adults care for young offspring that are not their own, a phenomenon called alloparenting. However, most nonparental adults must be sensitized by repeated or extended exposures to newborns before they will robustly display parental-like behaviors. To capture neurogenomic events underlying the transition to active parental caring behaviors, we analyzed brain gene expression and chromatin profiles of virgin female mice co-housed with mothers during pregnancy and after birth. After an initial display of antagonistic behaviors and a surge of defense-related gene expression, we observed a dramatic shift in the chromatin landscape specifically in amygdala of the pup-exposed virgin females, accompanied by a dampening of anxiety-related gene expression. This epigenetic shift coincided with hypothalamic expression of the oxytocin gene and the emergence of behaviors and gene expression patterns classically associated with maternal care. The results outline a neurogenomic program associated with dramatic behavioral changes and suggest molecular networks relevant to human postpartum mental health.

animal behavior and cognition↗

bioRxiv2017

Cross-species systems analyses reveal a conserved brain transcriptional response to social challenge

Social challenges like territorial intrusions evoke behavioral responses in widely diverging species. Recent work has revealed 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 multi-species 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 sub-networks. 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 reveals systems-level mechanisms that have been repeatedly co-opted during evolution of analogous behaviors, thus advancing the genetic toolkit concept beyond individual genes.

genomics↗