Project description:The gut-brain axis allows gut microbes to influence host social behavior, yet the specific role of microbial genetic variation in this process and its potential transgenerational effects remains poorly understood. Using C. elegans as a model, we identified 77 E. coli strains among 3,983 mutants that markedly enhanced C. elegans aggregation behavior. Our findings reveal that mutant bacteria modulate C. elegans social behavior through distinct neurobehavioral pathways, demonstrating a synergistic regulatory mechanism between microbial genetics and host heredity. Mechanistically, ycgJ mutant bacteria were found to impact C. elegans social behavior via the mitochondrial pathway. Additionally, even F2 offspring of parent C. elegans exposed to these mutant bacteria exhibited enhanced social behavior within their populations. These insights underscore the significance of investigating microbial genetic variation in relation to host behavior, particularly for the development of genetically engineered probiotics, aimed at promoting well-being across generations.
Project description:This SuperSeries is composed of the following subset Series: GSE33090: Dramatic effects of social behavior on gene regulation in rhesus macaques [Individual_expression] GSE34127: Dramatic effects of social behavior on gene regulation in rhesus macaques [Cell type_expression] GSE34128: Dramatic effects of social behavior on gene regulation in rhesus macaques [Bisulfite_seq] Refer to individual Series
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:Human infants exhibit innate social behaviors at birth, yet little is understood about the embryonic development of sociality. We screened 1120 known drugs and found that embryonic inhibition of topoisomerase IIα (Top2a) resulted in lasting social deficits in zebrafish. In mice, prenatal Top2 inhibition caused behavioral defects related to core symptoms of autism, including impairments in social interaction and communication. Mutation of Top2a in zebrafish caused downregulation of a set of genes highly enriched for genes associated with autism in humans. Both the Top2a-regulated and autism-associated gene sets possess binding sites for polycomb repressive complex 2 (PRC2), a regulatory complex responsible for H3K27 trimethylation. Moreover, both gene sets are highly enriched for H3K27me3. Inhibition of PRC2 component Ezh2 rescued social deficits caused by Top2 inhibition. Therefore, Top2a is a key component of an evolutionarily conserved pathway that promotes the development of social behavior through PRC2 and H3K27me3.
Project description:Genetic disruptions of the forkhead box transcription factor FOXP2 in humans cause an autosomal-dominant speech and language disorder. While FOXP2 expression pattern are highly conserved, its role in specific brain areas for mammalian social behaviors remains largely unknown. Here we studied mice carrying a homozygous cortical Foxp2 deletion. The postnatal development and gross morphological architecture of mutant mice was indistinguishable from wildtype (WT) littermates. Unbiased behavioral profiling of adult mice revealed abnormalities in approach behavior towards conspecifics as well as in the reciprocal responses of WT interaction partners. Furthermore mutant mice showed alterations in acoustical parameters of ultrasonic vocalizations (USV), which also differed in function of the social context. Cell type-specific gene expression profiling of cortical pyramidal neurons revealed aberrant regulation of genes involved in social behavior. In particular Foxp2 mutants showed the downregulation of Mint2 (Apba2), a gene involved in approach behavior in mice and autism spectrum disorder in humans. Taken together these data demonstrate that cortical Foxp2 is required for normal social behaviors in mice.
Project description:Early life stress (ELS), such as neglect and maltreatment, exhibits a strong impact on the mental and brain development of children. However, it is not fully understood how ELS affects the function in developing prefrontal cortex (PFC). In this study, we performed social isolation on weaned pre-adolescent mice and investigated how ELS could affect the function in behavior and transcriptome in PFC. We found that reductions of social interaction, social preference, and social novelty in ELS mice. Moreover, an increase of anxiety-like behavior was observed in ELS mice, but there were no changes in weight and repetitive behavior. To identify the gene involved in social behavior, we conducted transcriptome analysis and identified 15 differentially expressed genes (DEGs) in the PFC of ELS mice. These genes were involved in transcriptional regulation, stress, and synaptic signaling. We also found that a decreased number of neurons and an increased number of microglia in the PFC of ELS mice. These results suggest that ELS affects PFC cytoarchitecture by stress signal transduction and eventually alters mouse behavior. Our study demonstrates that ELS influences behavior, transcriptome and cytoarchitecture in the brain of adolescent mice.