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Integrating Reproductive States and Social Cues in the Control of Sociosexual Behaviors (scRNAseq data)

ABSTRACT: Female sociosexual behaviors, essential for survival and reproduction, are modulated by ovarian hormones and triggered in the context of appropriate social cues. Here we identify primary estrous-sensitive Cacna1h-expressing medial prefrontal cortex (mPFCCacna1h+) neurons that integrate hormonal states with recognition of potential mates to orchestrate these complex cognitive behaviors. Bidirectional manipulation of mPFCCacna1h+ neurons shifts opposite-sex-directed social behaviors between estrus and diestrus females via anterior hypothalamic outputs. In males, these neurons serve opposite functions compared to estrus females. Miniscope imaging reveals mixed-representation of self-estrous states and social target sex in distinct mPFCCacna1h+ subpopulations, with biased-encoding of opposite-sex cues in estrus females and males. Mechanistically, ovarian hormone-induced Cacna1h upregulation enhances T-type rebound excitation after oxytocin inhibition, driving estrus-specific activity changes and the sexually dimorphic function of mPFCCacna1h+ neurons. These findings uncover a prefrontal circuit that integrates internal hormonal states and target-sex information to exert sexually bivalent top-down control over adaptive social behaviors.

ORGANISM(S): Mus musculus

PROVIDER: GSE227852 | GEO | 2025/05/20

REPOSITORIES: GEO

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Integrating Reproductive States and Social Cues in the control of Sociosexual Behaviors

Project description:Female sociosexual behaviors, essential for survival and reproduction, are adaptively modulated by ovarian hormones and triggered in the context of appropriate external social cues. Here we identify primary estrous-sensitive Cacna1h-expressing medial prefrontal (mPFCCacna1h+) neurons that integrate hormonal states with recognition of potential mates to orchestrate these complex cognitive behaviors. Bidirectional manipulation of mPFCCacna1h+ neurons drives opposite-sex-directed behavioral shifts between estrus and diestrus females via anterior hypothalamic outputs. In males, these neurons serve opposite functions compared to estrus females. Miniscope imaging reveals mixed-representation of self-estrous states and social target sex in distinct mPFCCacna1h+ subpopulations, with biased-encoding of opposite-sex social cues in estrus females and males. Mechanistically, ovarian hormone-driven upregulation of Cacna1h-encoded T-type calcium channels underlies estrus-specific activity changes and sexual-dimorphic function of mPFCCacna1h+ neurons. These findings uncover a prefrontal circuit that integrates internal hormonal states and target-sex information to exert sexually bivalent top-down control over adaptive social behaviors.

2025-05-20 | GSE283376 | GEO

The influence of the estrous cycle on sex differences in the rat adult medial prefrontal cortex transcriptome [ChIP-Seq]

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The influence of the estrous cycle on sex differences in the rat adult medial prefrontal cortex transcriptome [RNA-Seq]

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The influence of the estrous cycle on sex differences in the rat adult medial prefrontal cortex transcriptome [ChIP-Seq]

Project description:Hormonal fluctuations throughout the ovarian cycle contribute to femalesâ?? higher vulnerability to anxiety disorders when compared to males. Notably, such sex differences are controlled by regulation of genes in the medial prefrontal cortex (mPFC) including the transcription factor early growth response 1 (Egr1) in rats, which highlights a control of anxiety-like behaviors by sexually-biased gene expression. We therefore undertook a large-scale characterization of sex differences and their interaction with the estrous cycle in the adult mPFC transcriptome and report that proestrus and diestrus females (with high and low ovarian hormones levels, respectively) exhibited a partly-opposed sexually-biased transcriptome. Surprisingly, the extent of regulations within females vastly exceeded sex differences, and support a multi-level reorganization of synaptic function across the estrous cycle. Furthermore, genome-wide analysis of Egr1 binding highlighted its role in controlling the synapse-related genes varying within females, and the sex- and estrous cycle-dependent transcriptomic reorganization in the rat mPFC. Early growth response 1 (Egr1) binding profiling in the adult rat medial prefrontal cortex of males, proestrus females, and diestrus females. A total of 9 animals were used, corresponding to 3 Males, 2 proestrus females, and 4 diestrus females.

2015-10-23 | E-GEOD-69772 | biostudies-arrayexpress

The influence of the estrous cycle on sex differences in the rat adult medial prefrontal cortex transcriptome [RNA-Seq]

Project description:Hormonal fluctuations throughout the ovarian cycle contribute to femalesâ higher vulnerability to anxiety disorders when compared to males. Notably, such sex differences are controlled by regulation of genes in the medial prefrontal cortex (mPFC) including the transcription factor early growth response 1 (Egr1) in rats, which highlights a control of anxiety-like behaviors by sexually-biased gene expression. We therefore undertook a large-scale characterization of sex differences and their interaction with the estrous cycle in the adult mPFC transcriptome and report that proestrus and diestrus females (with high and low ovarian hormones levels, respectively) exhibited a partly-opposed sexually-biased transcriptome. Surprisingly, the extent of regulations within females vastly exceeded sex differences, and support a multi-level reorganization of synaptic function across the estrous cycle. Furthermore, genome-wide analysis of Egr1 binding highlighted its role in controlling the synapse-related genes varying within females, and the sex- and estrous cycle-dependent transcriptomic reorganization in the rat mPFC. mRNA profiling of 2-3 month-old males and females Sprague-Dawley rats in either Proestrus or Diestrus. A total of 11 samples were analyzed, corresponding to 4 males, 3 proestrus females, and 4 diestrus females.

2015-10-23 | E-GEOD-69765 | biostudies-arrayexpress

Transcriptional response across estrous in the mouse dorsal hippocampus is dysregulated by Cnih3 mutation

Project description:The hippocampus is a critical brain region for coordinating learning, memory, and behavior. In adult females, the estrus cycle alters these functions through the activity of steroids hormones, with well-characterized effects on cellular physiology and behavior. However,the molecular genetic basis of these outcomes has not been systematically explored. In order to better understand the role of sex and the estrous cycle in the hippocampus, we profiled the transcriptome of hippocampi from female mice in each stage of the estrus cycle, along with those of males. We identify only subtle sex differences in gene expression between the sexes on average, yet comparing males to individual estrous stages reveals ~100 genes deviating from male expression patterns at one point in their cyclic fluctuations across estrous cycle. These estrus-responsive genes are especially enriched in oligodendrocytes and glycinergic neurons, and are potentially regulated downstream of estrogen receptor repressed pathways. To further understand our previous observations of female- and estrous-specific behavioral outcomes in knockout of Cnih3, we performed the same profiling in the knockout strain. Surprisingly, Cnih3 knockouts showed far broader transcriptomic differences between estrous cycle stages and males, despite very subtle within-group-across-genotype expression changes. We show that Cnih3 knockout drives expression changes in opposing directions between males and all points of the estrous cycle, extensively accentuating the magnitude of sex-differential hippocampal gene expression compared to wild-types. We thus provide a novel resource characterizing estrous-specific gene expression patterns in the adult hippocampus, which can provide insights into mechanisms of sex differential neuropsychiatric functions and dysfunctions, and identify a role for Cnih3 in buffering the female brain against the transcriptional effects of estrous.

2023-02-17 | GSE199722 | GEO

Chronic stress and its effects on behavior, RNA expression of the bed nucleus of the stria terminalis, and the M-current of NPY neurons

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2023-12-05 | GSE235108 | GEO

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Project description:Social play is a well-conserved, dynamic behavior known to be sexually differentiated. In most species, males play more than females, a sex difference largely driven by the medial amygdala (MeA) yet the full mechanism establishing this bias is unknown. Here, we explore “the transcriptome of playfulness” in both sexes for the first time, demonstrating that the transcriptomic profile in the juvenile rat MeA associated with playfulness is markedly distinct in males and females. Parallel single-cell RNA-sequencing experiments from newborn rats suggest that inhibitory neurons drive this sex difference. Furthermore, we show that inhibitory neurons comprise the majority of play-active cells in the juvenile MeA, with males having more play-active cells than females, of which a greater proportion are GABAergic. Through integrative bioinformatic analyses, we further explore the expression, function, and cell-type specificity of key play-associated gene modules, providing valuable insight into the sex-biased mechanisms underlying this fundamental social behavior.

2025-04-23 | GSE295418 | GEO

The “play transcriptome” is sex-specific in the juvenile rat medial amygdala: a role for inhibitory neurons

2025-04-18 | GSE294410 | GEO

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