Biology subjects

Curley, J. P.

Publications and source records attributed to Curley, J. P..

6 recordsLinked to original sources

bioRxiv2025

Social Processing in the Amygdala: Single-Nucleus RNA-Sequencing Reveals Distinct Neuronal Responses to Dominant and Subordinate Cues

The amygdala serves as a critical neural hub for interpreting social cues, with its distinct subregions and diverse neuronal populations playing specialized roles in processing these signals. This study employs single-nucleus RNA sequencing (snRNA-seq) to characterize the amygdalas neuronal responses to olfactory cues associated with social dominance, uncovering distinct activation patterns within glutamatergic and GABAergic populations. We find that a glutamatergic cluster, characterized by expression patterns closely aligned with glutamatergic Slc17a7 (VGLUT1) medial amygdala (MeA) neurons, preferentially responds to dominant cues. In contrast, a larger glutamatergic Slc17a6 (VGLUT2) cluster associated with neurons of the MeA, as well as cortical and basomedial amygdala, exhibits a heightened response to subordinate cues, underscoring the MeA regions role in processing social olfactory information. Additionally, a glutamatergic cluster resembling dorsal endopririform (EPd) neurons responded more to dominant stimuli, supporting the EPds role in olfactory perception. We also identified a GABAergic cluster with elevated dopamine receptor 2 (Drd2) expression that predominantly responds to dominant cues, consistent with this receptors known role in mediating threat responses. Through gene co-expression network analysis, we linked gene expression within neuronal clusters to specific biological processes. These findings reveal distinct neuronal and molecular mechanisms underlying social processing, particularly in response to dominant and subordinate olfactory signals, thus enhancing our understanding of the neural substrates of social behavior.

neuroscience↗

bioRxiv2024

Capturing Dynamic Neuronal Responses to Dominant and Subordinate Social Hierarchy Members with catFISH

Dominance hierarchies are key to social organization in group-living species, requiring individuals to recognize their own and others ranks. This is particularly complex for intermediate-ranking animals, who navigate interactions with higher- and lower-ranking individuals. Using in situ hybridization, we examined how the brains of intermediate-ranked mice in hierarchies respond to dominant and subordinate stimuli by labeling activity-induced immediate early genes and neuronal markers. We show that distinct neuronal populations in the amygdala and hippocampus respond differentially across social contexts. In the basolateral amygdala, glutamatergic Slc17a7+ neurons, particularly dopamine-receptive Slc17a7+Drd1+ neurons, show elevated IEG expression in response to social stimuli, with a higher response to dominant over subordinate animals. Similar patterns are observed among Slc17a7+Oxtr+ neurons in the dorsal endopiriform nucleus and GABAergic Slc32a+ neurons in the medial amygdala. We also identified distinct neural ensembles selectively active in response to dominant and subordinate hierarchy members. We find a higher degree of reactivation among Slc17a7+Oxtr+ ensembles in the dorsal endopiriform nucleus in animals repeatedly presented with the same hierarchy member, as opposed to those presented with a dominant and subordinate member. We observe a similar pattern among Oxtr+ neurons in the dentate gyrus hilus, while the inverse is observed among Slc17a7+ Avrp1b+Oxtr+ neurons in the distal CA2CA3 region. Collectively, our findings reveal how social context is associated with activity changes in social, olfactory, and memory systems in the brain at the neuronal cell type level. This work lays the foundation for further precise cell-type investigation into how the brain processes social information.

neuroscience↗

bioRxiv2021

Distinct inflammatory and transcriptomic profiles in dominant versus subordinate males in mouse social hierarchies

Social status is a critical factor determining health outcomes in human and nonhuman social species. In social hierarchies with reproductive skew, individuals compete to monopolize resources and increase mating opportunities. This can come at a significant energetic cost leading to trade-offs between different physiological systems. Particularly, changes in energetic investment in the immune system can have significant short and long-term effects on fitness and health. We have previously found that dominant alpha male mice living in social hierarchies have increased metabolic demands related to territorial defense. In this study, we tested the hypothesis that high-ranking male mice favor energetically inexpensive adaptive immunity, while subordinate mice show higher investment in innate immunity. We housed 12 groups of 10 outbred CD-1 male mice in a social housing system. All formed linear social hierarchies and subordinate mice had higher concentrations of plasma corticosterone (CORT) than alpha males. This difference was heightened in highly despotic hierarchies. Using flow cytometry, we found that dominant status was associated with a significant shift in immunophenotypes towards favoring adaptive versus innate immunity. Using Tag-Seq to profile hepatic and splenic transcriptomes of alpha and subordinate males, we identified genes that regulate metabolic and immune defense pathways that are associated with status and/or CORT concentration. In the liver, dominant animals showed an up-regulation of specific genes involved in major urinary production and catabolic processes, whereas subordinate animals showed an up-regulation of genes promoting biosynthetic processes, wound healing, and proinflammatory responses. In spleen, subordinate mice showed up-regulation of genes facilitating oxidative phosphorylation and DNA repair and CORT was negatively associated with genes involved in lymphocyte proliferation and activation. Together, our findings suggest that dominant and subordinate animals adaptively shift energy investment in immune functioning and gene expression to match their contextual energetic demands. HighlightsO_LIImmunity is shaped by stress and energetic pressures associated with social status C_LIO_LIDominant and subordinate mice favor adaptive and innate immunity, respectively C_LIO_LIDominants increase expression of genes involved in energy production C_LIO_LIWound healing and DNA repair genes are upregulated in subordinates C_LIO_LIGenes related to maintaining and signaling social status are upregulated in dominants C_LI

immunology↗

bioRxiv2020

Effect of relative social rank within a social hierarchy on neural activation in response to familiar or unfamiliar social signals

Competent social functioning of group-living species relies on the ability of individuals to detect and utilize conspecific social cues to guide behavior. Previous studies have identified numerous brain regions involved in processing these external cues, collectively referred to as the Social Decision-Making Network. However, how the brain encodes social information with respect to an individuals social status has not been thoroughly examined. In mice, cues about an individuals identity, including social status, are conveyed through urinary proteins. In this study, we assessed the neural cFos immunoreactivity in dominant and subordinate male mice exposed to familiar and unfamiliar dominant and subordinate male urine. The posteroventral medial amygdala was the only brain region that responded exclusively to dominant compared to subordinate male urine. In all other brain regions, including the VMH, PMv, and vlPAG, activity is modulated by a combination of odor familiarity and the social status of both the urine donor and the subject receiving the cue. We show that dominant subjects exhibit robust differential activity across different types of cues compared to subordinate subjects, suggesting that individuals perceive social cues differently depending on social experience. These data inform further investigation of neurobiological mechanisms underlying social-status related brain differences and behavior.

neuroscience↗

bioRxiv2019

Social hierarchy position in female mice is associated with plasma corticosterone levels and hypothalamic gene expression

Social hierarchies emerge when animals compete for access to resources such as food, mates or physical space. Wild and laboratory male mice have been shown to develop linear hierarchies, however, less is known regarding whether female mice have sufficient intrasexual competition to establish significant social dominance relationships. In this study, we examined whether groups of outbred CD-1 virgin female mice housed in a large vivaria formed social hierarchies. We show that females use fighting, chasing and mounting behaviors to rapidly establish highly directionally consistent social relationships. Notably, these female hierarchies are less linear, steep and despotic compared to male hierarchies. Female estrus state was not found to have a significant effect on aggressive behavior, though dominant females had elongated estrus cycles (due to increased time in estrus) compared to subordinate females. Plasma estradiol levels were equivalent between dominant and subordinate females. Subordinate females had significantly lower levels of basal corticosterone compared to dominant females. Analyses of gene expression in the ventromedial hypothalamus indicated that subordinate females have elevated ER, ER{beta} and OTR mRNA compared to dominant females. This study provides a methodological framework for the study of the neuroendocrine basis of female social aggression and dominance in laboratory mice.

animal behavior and cognition↗

bioRxiv2018

Immediate early gene activation throughout the brain is associated with dynamic changes in social context

Social competence is dependent on successful processing of social context information. The social opportunity paradigm is a methodology in which dynamic shifts in social context are induced through removal of the alpha male in a dominance hierarchy, leading to rapid ascent in the hierarchy of the beta male and of other subordinate males in the social group. In the current study, we use the social opportunity paradigm to determine what brain regions respond to this dynamic change in social context, allowing an individual to recognize the absence of the alpha male and subsequently perform status-appropriate social behaviors. Replicating our previous work, we show that following removal of the alpha male, beta males rapidly ascend the social hierarchy and attain dominant status by increasing aggression towards more subordinate individuals. Analysis of patterns of Fos immunoreactivity throughout the brain indicates that in individuals undergoing social ascent, there is increased activity in regions of the social behavior network, as well as the infralimbic and prelimbic regions of the prefrontal cortex and areas of the hippocampus. Our findings demonstrate that male mice are able to respond to changes in social context and provide insight into the how the brain processes these complex behavioral changes.

animal behavior and cognition↗