Project description:Background Appropriate social interactions influence animal fitness by impacting several processes, such as mating, territory defense, and offspring care. Many studies shedding light on the neurobiological underpinnings of social behavior have focused on nonapeptides (vasopressin, oxytocin, and homologues) and on sexual or parent-offspring interactions. Furthermore, animals have been studied under artificial laboratory conditions, where the consequences of behavioral responses may not be as critical as when expressed under natural environments, therefore obscuring certain physiological responses. We used automated recording of social interactions of wild house mice outside of the breeding season to detect individuals at both tails of a distribution of egocentric network sizes (characterized by number of different partners encountered per day). We then used RNA-seq to perform an unbiased assessment of neural differences in gene expression in the prefrontal cortex, the hippocampus and the hypothalamus between these mice with naturally occurring extreme differences in social network size. Results We found that the neurogenomic pathways associated with having extreme social network sizes differed between the sexes. In females, hundreds of genes were differentially expressed between animals with small and large social network sizes, whereas in males very few were. In males, X-chromosome inactivation pathways in the prefrontal cortex were the ones that better differentiated animals with small from those with large social network sizes animals. In females, animals with small network size showed up-regulation of dopaminergic production and transport pathways in the hypothalamus. Additionally, in females, extracellular matrix deposition on hippocampal neurons was higher in individuals with small relative to large social network size. Conclusions Studying neural substrates of natural variation in social behavior in traditional model organisms in their habitat can open new targets of research for understanding variation in social behavior in other taxa.
Project description:Public information is widely available at low cost to animals living in social groups. For instance, bystanders may eavesdrop on signaling interactions between conspecifics and use it to adapt their subsequent behavior towards the observed individuals. This social eavesdropping ability is expected to require specialized mechanisms such as social attention, which selects social information available for learning. To begin exploring the genetic basis of social eavesdropping, we used a previously established attention paradigm in the lab to study the brain gene expression profile of male zebrafish in relation to the attention they have paid towards conspecifics involved or not involved in agonistic interactions. Microarray gene chips were used to characterize their brain transcriptomes based on differential expression of single genes and gene sets. These analyses were complemented by promoter region-based techniques. Using data from both approaches, we further drafted protein interaction networks. Our results suggest that attentiveness towards conspecifics, whether interacting or not, activates pathways linked to neuronal plasticity and memory formation. The network analyses suggested that fos and jun are key players on this response, and that npas4a, nr4a1 and egr4 may also play an important role. Furthermore, specifically observing fighting interactions further triggered pathways associated to a change in the alertness status (dnajb5) and to other genes related to memory formation (btg2, npas4b), which suggests that the acquisition of eavesdropped information about social relationships activates specific processes on top of those already activated just by observing conspecifics.
Project description:Social behaviors are essential for survival and reproduction and vary strongly among individuals, species, and heritable brain diseases. The molecular and cellular bases of this variation are poorly resolved, and discovering them is necessary to understand how neural circuit and behavioral functions—and dysfunctions—vary in social contexts. Here we integrate single nucleus RNA-sequencing (snRNA-seq) with comparative genomics and automated behavior analysis to investigate the neurobiology of castle-building, a recently-evolved social, spatial, goal-directed, and repetitive construction behavior in Lake Malawi cichlid fishes. We simultaneously control for and analyze two biological variables correlated with castle-building behavior: quivering, a courtship “dance” behavior, and relative gonadal mass. We find signatures of building-, quivering-, and gonadal-associated neuronal excitation, gene expression, and neurogenesis in distinct cell populations. Converging lines of evidence support the involvement of estrogen, TrkB, and CCK signaling systems, and specific pallial excitatory neuronal subpopulations, in castle-building behavior. We show additional evidence that castle-building has evolved in part through genomic divergence in a gene module that is selectively expressed in stem-like quiescent radial glial cells (RGCs) lining the ventricular zone of the pallium. This RGC subpopulation exhibits signatures of a building-associated departure from quiescence, which in turn is associated with neuronal rebalancing in the putative fish homologue of the hippocampus. Our work supports an unexpected role for glia and neurogenesis in the evolution of social behavior, and more broadly shows how snRNA-seq can be used to systematically profile the cellular bases of previously unstudied social behaviors in new species systems.
Project description:Social behaviors are essential for survival and reproduction and vary strongly among individuals, species, and heritable brain diseases. The molecular and cellular bases of this variation are poorly resolved, and discovering them is necessary to understand how neural circuit and behavioral functions—and dysfunctions—vary in social contexts. Here we integrate single nucleus RNA-sequencing (snRNA-seq) with comparative genomics and automated behavior analysis to investigate the neurobiology of castle-building, a recently-evolved social, spatial, goal-directed, and repetitive construction behavior in Lake Malawi cichlid fishes. We simultaneously control for and analyze two biological variables correlated with castle-building behavior: quivering, a courtship “dance” behavior, and relative gonadal mass. We find signatures of building-, quivering-, and gonadal-associated neuronal excitation, gene expression, and neurogenesis in distinct cell populations. Converging lines of evidence support the involvement of estrogen, TrkB, and CCK signaling systems, and specific pallial excitatory neuronal subpopulations, in castle-building behavior. We show additional evidence that castle-building has evolved in part through genomic divergence in a gene module that is selectively expressed in stem-like quiescent radial glial cells (RGCs) lining the ventricular zone of the pallium. This RGC subpopulation exhibits signatures of a building-associated departure from quiescence, which in turn is associated with neuronal rebalancing in the putative fish homologue of the hippocampus. Our work supports an unexpected role for glia and neurogenesis in the evolution of social behavior, and more broadly shows how snRNA-seq can be used to systematically profile the cellular bases of previously unstudied social behaviors in new species systems.
Project description:The lateral habenula (LHb) is an essential hub brain region modulating the monoamine system such as dopamine, serotonin. Hyperactivity of LHb has implications for psychiatric disorders such as depression, anxiety, and schizophrenia, which are commonly associated with social dysfunction. However, the role of LHb in social behavior has remained elusive. Here, we find that experiencing acute social isolation affects synaptic function in LHb and social behavior. After acute social isolation, long-term depression (LTD) in LHb is impaired and rescued by activating the 5-HT4 receptor (5-HT4R). Indeed, Htr4 expression in LHb is up-regulated following acute social isolation. Finally, acute social isolation enhances the social preference for familiars such as housing-mates to stranger conspecifics. Consistent with electrophysiological results, pharmacological activation of 5-HT4R in LHb restored innate social preference. These results suggest that acute social isolation influences social decisions with 5-HT4R-dependent synaptic modification in LHb.
Project description:Social stress mouse models were used to simulate human post-traumatic stress disorder (PTSD). C57B/6 mice exposed to SJL aggressor mice exhibited behaviors accepted as PTSD-in-mouse phenotype: 'frozen' motion, aggressor's barrier avoidance, startled jumping, and retarded locomotion. Transcripts in spleen, blood and hemi-brain of stressed and control C57B/6 mice were analyzed using Agilent's mouse genome-wide arrays. C57B6 mice were exposed to SJL aggressor mice for periods of 5 days and 10 days (6 hours each day) to induce anxiety/stress which parallels to PTSD in human. Organs, blood and brain regions were collected after 24 hours and 1.5 week of post 5 days social defeat period; and 24 hour and 6 weeks post 10 days social stress period.
Project description:Social experiences are an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a pro-inflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here, we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-κB dependent pro-inflammatory pathways and lower expression of genes involved in the antiviral response and type I interferon (IFN) signaling (see Snyder-Mackler et al. Science, 2016 doi:10.1126/science.aah3580 and GSE83304). Here we show that, counter to predictions, low status drives more exaggerated expression of both NF-κB and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are not only linked to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history – in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.