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Curley, J.

Publications and source records attributed to Curley, J..

6 recordsLinked to original sources

Socially dominant male mice in social hierarchies identified via automated RFID tracking exhibit elevated activity levels and circulating markers of higher metabolic demand

Dominance hierarchies are a fundamental aspect of social organization, enabling animals to minimize aggression and optimize access to resources. Previous studies have highlighted the energetic and physiological demands of dominant status, as well as the behavioral flexibility required of subordinates to navigate these hierarchies. Despite advancements in automated behavior tracking, limitations persist in tracking fine-scale, real-time interactions within complex social environments. Here, we developed and validated a novel RFID-based system to continuously monitor dominance hierarchies in group-housed male mice over 10 days. This system enabled unbiased behavioral inference across light phases and revealed spatial and temporal patterns of dominance behavior undetectable through traditional live-scored methods. Automated tracking accurately identified alpha individuals and consistently inferred linear hierarchies across cohorts, with greater precision for higher-ranked individuals. Behavioral metrics, such as transition frequencies and proximity to food zones, were consistent with dominance driven activity. Hormonal analyses revealed that higher-ranked mice exhibited increased leptin and peptide YY, consistent with heightened activity and satiety signaling, while lower C-peptide levels reflected greater metabolic demands of dominance. Furthermore, dominance rank was associated with differences in light-dark activity, which were in turn related to circulating hormone profiles. This study demonstrates the utility of automated RFID tracking in capturing dominance hierarchies with temporal and spatial granularity, while revealing links between social rank, metabolic regulation, and activity patterns advancing our understanding of social behavior dynamics.

animal behavior and cognition↗

Single-Nucleus Transcriptomics of the Mouse Medial Preoptic Area Reveals Sex-Dependent Molecular Signatures of Social Dominance

Social dominance hierarchies are a common form of social organization across animal species. We have previously shown that both male and female CD-1 mice form highly linear dominance hierarchies. In mice and other vertebrates, the medial preoptic area (mPOA) is a key hypothalamic sub-region regulating aggressive and defensive behaviors that support hierarchical social structures, but the transcriptional mechanisms in mPOA neurons underlying dominance behaviors and the influence of sex on these neuron populations in the context of social dominance hierarchies remain largely unresolved. Using single-nucleus RNA sequencing (snRNA-seq) to profile mPOA neurons from dominant and subordinate mice, we identified highly consistent social status-dependent changes in the transcriptomes of neuronal nuclei expressing neuropeptide transcripts. Oxytocin expression was remarkably widespread across mPOA neurons, and we found it to be the primary driver of group differences in neuropeptide co-expression networks. Overall, dominant males and females exhibited markedly decreased expression of oxytocin and vasopressin and had a lower proportion of neurons co-expressing multiple neuropeptide transcripts compared to subordinate individuals. In contrast, subordinates displayed widespread reorganization of the transcriptomic neuropeptidome and strikingly enhanced coupling of neuropeptide expression in mPOA neurons. Despite the strong pattern of concordant gene expression in dominant and subordinate individuals, the number of genes that were differentially expressed by status was substantially reduced in males compared to females. In sum, these results demonstrate that maintenance of social status dynamically reconfigures hypothalamic transcriptomic neuropeptidome in a sex-dependent manner and establishes how social status is encoded at a single-cell resolution.

neuroscience↗

Rapid changes in cholinergic signaling, myelination and thyroid signaling pathway gene expression in amygdala subnuclei in response to social status maintenance and reorganization

Male CD-1 mice form linear social hierarchies and can rapidly reform them following social reorganization. Through Tag-based sequencing in the medial amygdala (MeA), we identified several genes regulating cholinergic signaling, myelination, and thyroid signaling that rapidly shift expression 70 minutes after animals change social status. Here, we further characterize the expression patterns of individual genes within these pathways in both stable and reorganized hierarchies. We find that genes related to cholinergic signaling show higher expression in the MeA of dominant males in stable hierarchies as well as when reestablishing dominance in reorganized hierarchies. Dominant males also show higher levels of myelination related genes than socially descending males when reestablishing their social status during social reorganization but less so in stable groups. Conversely, thyroid signaling genes show higher expression in the MeA in subordinate males and previously dominant males who are socially descending. Using RNAscope, we were able to demonstrate broadly similar patterns of gene expression immediately following social reorganization across the MeA, basolateral, and central amygdala for 7 genes of interest (chat, slc5a7, ache, mbp, mog, crym, mybpc1). High levels of co-expression of cholinergic signaling and myelination gene expression in dominant males suggest that these processes work together to promote resilience to the social challenge and promote dominance. In summary, we demonstrate that rapid changes in amygdala gene expression in each pathway are associated with the formation and maintenance of dominance and subordinate social status in stable and reorganized environments.

neuroscience↗

Rapid changes in plasma corticosterone and medial amygdala transcriptome profiles during social status change reveal molecular pathways associated with a major life history transition in mouse dominance hierarchies

Social hierarchies are a common form of social organization across species. Although hierarchies are largely stable across time, animals may socially ascend or descend within hierarchies depending on environmental and social challenges. Here, we develop a novel paradigm to study social ascent and descent within male CD-1 mouse social hierarchies. We show that mice of all social ranks rapidly establish new stable social hierarchies when placed in novel social groups with animals of equivalent social status. Seventy minutes following social hierarchy formation, previously socially dominant animals exhibit higher increases in plasma corticosterone and vastly greater transcriptional changes in the medial amygdala (MeA), which is central to the regulation of social behavior, compared to previously subordinate animals. Specifically, social descent is associated with reductions in MeA expression of myelination and oligodendrocyte differentiation genes. Maintaining high social status is associated with high expression of genes related to cholinergic signaling in the MeA. Conversely, social ascent is related to relatively few unique rapid changes in the MeA. We also identify novel genes associated with social transition that show common changes in expression when animals undergo either social descent or social ascent compared to maintaining their status. Two genes, Myosin binding protein C1 (Mybpc1) and -Crystallin (Crym), associated with vasoactive intestinal polypeptide (VIP) and thyroid hormone pathways respectively, are highly upregulated in socially transitioning individuals. Further, increases in genes associated with synaptic plasticity, excitatory glutamatergic signaling and learning and memory pathways were observed in transitioning animals suggesting that adaptations in these processes may support rapid social status changes. Author SummaryWe investigate how male CD-1 mice behaviorally, physiologically, and molecularly respond to changes in their social hierarchies. We found that mice rapidly reform social hierarchies when placed into novel social groups. Formerly dominant mice experience the greatest increase in stress hormone levels and the largest shifts in gene expression in the medial amygdala, a brain region crucial for regulating social behavior. Specifically, we observed reduced expression of genes related to myelin production and maintenance as well as cholinergic functioning in formerly dominant males who socially descended. In contrast, formerly subordinate males who socially ascended displayed fewer genomic changes. Moreover, we identified a set of genes that change expression when animals transition their social status regardless of whether they rise or fall in rank. These social transition genes provide new insights into the biological mechanisms underpinning social plasticity. Our findings demonstrate the distinct molecular mechanisms that are shared between socially ascending versus descending mice, as well as those that are unique to each type of social transition.

neuroscience↗

Temporal microstructure of dyadic social behavior during relationship formation in mice

Understanding the temporal dynamics of how unfamiliar animals establish dominant-subordinate relationships and learn to modify their behavior in response to their social partner in context-appropriate manners is critical in biomedical research concerning social competence. Here we observe and analyze the microstructure of social and non-social behaviors as 21 pairs of outbred CD-1 male mice (Mus Musculus) establish dominant-subordinate relationships during daily 20-minute interaction for five consecutive days. Using Kleinberg burst detection algorithm, we demonstrate aggressive and subordinate interactions occur in bursting patterns followed by quiescence period rather than in uniformly distributed across social interactions. Further, we identify three phases of dominant-subordinate relationship development (pre-, middle-, and post-resolution) by combining phi-coefficient and difference methods used to determine at which bursting event mice resolve dominant-subordinate relationships. Using First Order Markov Chains within individuals we show dominant and subordinate animals establish significantly different behavioral repertoire once they resolve the relationships. In both dominant and subordinate mice, the transitions between investigative and agonistic behavior states are not common. Lastly, we introduce Forward Spike Time Tiling Coefficient, the strength of association between the given behavior of one individual with the target behavior of the other individual within a specified time window. With this method, we describe the likelihood of a mouse responding to a behavior with another behavior differ in pre- and post-resolution phases. The data suggest that subordinate mice learn to exhibit subordinate behavior in response to dominant partners behaviors while dominant mice become less likely to show subordinate behaviors in response to their partners action. Overall, with the tool we present in this study, the data suggest CD-1 male mice are able to establish dominance relationships and modify their behaviors even to the same social cues under different social contexts competently.

animal behavior and cognition↗

Social status in mouse social hierarchies is associated with variation in oxytocin and vasopressin 1a receptor densities

The neuropeptides oxytocin and vasopressin and their receptors have established roles in the regulation of mammalian social behavior including parental care, sex, affiliation and pair-bonding, but less is known regarding their relationship to social dominance and subordination within social hierarchies. We have previously demonstrated that male mice can form stable linear dominance hierarchies with individuals occupying one of three classes of social status: alpha, subdominant, subordinate. Alpha males exhibit high levels of aggression and rarely receive aggression. Subdominant males exhibit aggression towards subordinate males but also receive aggression from more dominant individuals. Subordinate males rarely exhibit aggression and receive aggression from more dominant males. Here, we examined whether variation in social status was associated with levels of oxytocin (OTR) and vasopressin 1a (V1aR) receptor binding in socially relevant brain regions. We found that socially dominant males had significantly higher OTR binding in the nucleus accumbens core than subordinate animals. Alpha males also had higher OTR binding in the anterior olfactory nucleus, posterior part of the cortical amygdala and rostral lateral septum compared to more subordinate individuals. Conversely, alpha males had lower V1aR binding in the rostral lateral septum and lateral preoptic area compared to subordinates. These observed relationships have two potential explanations. Preexisting individual differences in the patterns of OTR and V1aR binding may underlie behavioral differences that promote or inhibit the acquisition of social status. More likely, the differential social environments experienced by dominant and subordinate animals may shift receptor expression, potentially facilitating the expression of adaptive social behaviors. HighlightsO_LIMice living in social hierarchies express different levels of oxytocin receptor (OTR) and vasopressin 1a receptor (V1aR) binding in various brain regions according to their social status. C_LIO_LIAlphas and subdominants have higher OTR binding in the nucleus accumbens compared to subordinates. C_LIO_LIAlphas have higher OTR binding in the anterior olfactory nucleus compared to subdominants and subordinates. C_LIO_LIAlphas have higher OTR and lower V1aR binding in the rostral lateral septum compared to subordinates. C_LIO_LIAlphas have lower V1aR binding in the lateral preoptic area compared to subordinates. C_LI

neuroscience↗