Cortical ensembles orchestrate social competition through hypothalamic outputs.

Most social species self-organize into dominance hierarchies1,2, which decreases aggression and conserves energy3,4, but it is not clear how individuals know their social rank. We have only begun to learn how the brain represents social rank5-9 and guides behaviour on the basis of this representation. The medial prefrontal cortex (mPFC) is involved in social dominance in rodents7,8 and humans10,11. Yet, precisely how the mPFC encodes relative social rank and which circuits mediate this computation is not known. We developed a social competition assay in which mice compete for rewards, as well as a computer vision tool (AlphaTracker) to track multiple, unmarked animals. A hidden Markov model combined with generalized linear models was able to decode social competition behaviour from mPFC ensemble activity. Population dynamics in the mPFC predicted social rank and competitive success. Finally, we demonstrate that mPFC cells that project to the lateral hypothalamus promote dominance behaviour during reward competition. Thus, we reveal a cortico-hypothalamic circuit by which the mPFC exerts top-down modulation of social dominance.

Distinct immune 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. In particular, 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 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 a relatively higher expression of specific genes involved in major urinary production and catabolic processes, whereas subordinate animals showed relatively higher expression of genes promoting biosynthetic processes, wound healing, and proinflammatory responses. In spleen, subordinate mice showed relatively higher expression 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 immune profiles and peripheral gene expression to match their contextual needs.

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.

Influence of maternal care on the developing brain: Mechanisms, temporal dynamics and sensitive periods.

Variation in maternal care can lead to divergent developmental trajectories in offspring with implications for neuroendocrine function and behavioral phenotypes. Study of the long-term outcomes associated with mother-infant interactions suggests complex mechanisms linking the experience of variation in maternal care and these neurobiological consequences. Through integration of genetic, molecular, cellular, neuroanatomical, and neuroendocrine approaches, significant advances in our understanding of these complex pathways have been achieved. In this review, we will consider the impact of maternal care on male and female offspring development with a particular focus on the issues of timing and mechanism. Identifying the period of sensitivity to maternal care and the temporal dynamics of the molecular and neuroendocrine changes that are a consequence of maternal care represents a critical step in the study of mechanism.

Major urinary protein levels are associated with social status and context in mouse social hierarchies.

We have previously shown that male mice living in groups of 12 males establish and maintain stable linear social hierarchies with each individual having a defined social rank. However, it is not clear which social cues mice use to signal and recognize their relative social status within their hierarchy. In this study, we investigate how individual social status both in pairs and in groups affects the levels of major urinary proteins (MUPs) and specifically MUP20 in urine. We housed groups of adult outbred CD1 male mice in a complex social environment for three weeks and collected urine samples from all individuals repeatedly. We found that dominant males produce more MUPs than subordinates when housed in pairs and that the production of MUPs and MUP20 is significantly higher in alpha males compared with all other individuals in a social hierarchy. Furthermore, we found that hepatic mRNA expression of Mup3 and Mup20 is significantly higher in alpha males than in subordinate males. We also show that alpha males have lower urinary creatinine levels consistent with these males urinating more than others living in hierarchies. These differences emerged within one week of animals being housed together in social hierarchies. This study demonstrates that as males transition to become alpha males, they undergo physiological changes that contribute to communication of their social status that may have implications for the energetic demands of maintaining dominance.

Dynamic changes in social dominance and mPOA GnRH expression in male mice following social opportunity.

Social competence - the ability of animals to dynamically adjust their social behavior dependent on the current social context - is fundamental to the successful establishment and maintenance of social relationships in group-living species. The social opportunity paradigm, where animals rapidly ascend a social hierarchy following the removal of more dominant individuals, is a well-established approach for studying the neural and neuroendocrine mechanisms underlying socially competent behavior. In the current study, we demonstrate that this paradigm can be successfully adapted for studying socially competent behavior in laboratory mice. Replicating our previous reports, we show that male laboratory mice housed in a semi-natural environment form stable linear social hierarchies. Novel to the current study, we find that subdominant male mice immediately respond to the removal of the alpha male from a hierarchy by initiating a dramatic increase in aggressive behavior towards more subordinate individuals. Consequently, subdominants assume the role of the alpha male. Analysis of brain gene expression in individuals 1h following social ascent indicates elevated gonadotropin-releasing hormone (GnRH) mRNA levels in the medial preoptic area (mPOA) of the hypothalamus compared to individuals that do not experience a social opportunity. Moreover, hormonal analyses indicate that subdominant individuals have increased circulating plasma testosterone levels compared to subordinate individuals. Our findings demonstrate that male mice are able to dynamically and rapidly adjust both behavior and neuroendocrine function in response to changes in social context. Further, we establish the social opportunity paradigm as an ethologically relevant approach for studying social competence and behavioral plasticity in mammals.

Temporal pairwise-correlation analysis provides empirical support for attention hierarchies in mice.

In many social hierarchies, more subordinate individuals adjust their behaviour according to the presence or behaviour of more dominant individuals. In this study, it is shown that male mice form linear dominance hierarchies characterized by individuals attacking in bursts. Temporal pairwise-correlation analysis reveals that non-dominant individuals avoid behaving aggressively concurrently with an aggressively behaving alpha male. This anti-correlation is only found with alpha males and is greater for more despotic alpha males. It is concluded that less dominant individuals modulate their aggressive behaviour in response to their social context, resulting in an attentional group structure.

Plasticity of the Maternal Brain Across the Lifespan.

Maternal behavior is dynamic and highly sensitive to experiential and contextual factors. In this review, this plasticity will be explored, with a focus on how experiences of females occurring from the time of fetal development through to adulthood impact maternal behavior and the maternal brain. Variation in postpartum maternal behavior is dependent on estrogen sensitivity within the medial preoptic area of the hypothalamus and activation within mesolimbic dopamine neurons. This review will discuss how experiences across the lifespan alter the function of these systems and the multigenerational consequences of these neuroendocrine and behavioral changes. These studies, based primarily on the examination of maternal behavior in laboratory rodents and nonhuman primates, provide mechanistic insights relevant to our understanding of human maternal behavior and to the mechanisms of lifelong plasticity.

Variations in maternal behavior in rats selected for infant ultrasonic vocalization in isolation.

Individual differences in maternal behavior in rodents are associated with altered physiology and behavior in offspring across their lifespan and across generations. Offspring of rat dams that engage in high frequencies of high-arched-back nursing and pup-licking (High-LG) show attenuated stress responses compared to those engaging in lower frequencies (Low-LG). Selective breeding also produces widespread alterations in physiology and behavior that are stable over generations. To examine processes underlying generational and developmental influences on anxiety in an animal model, we developed two lines of rats that emit either extremely high (High-USV) or low (Low-USV) rates of 45kHz ultrasonic vocalizations in isolation at postnatal day 10. Compared to the Low-USV line, High-USV rats display increased indices of anxiety- and depression-like behavior in adulthood. The current study assessed maternal behaviors as well as oxytocin and vasopressin receptor density in High-USV and Low-USV dams to determine if selective breeding had produced differences that paralleled those found in Low- and High-LG dams. We found that Low-USV dams engage in more high-arched nursing and pup-licking than High-USV dams. Differences in oxytocin and vasopressin receptor levels were not widespread throughout the brain, with line differences in the piriform cortex and nucleus accumbens. This research illustrates the potential interplay between genetically determined (USV line) and environmental (postnatal mother-infant interactions) factors in accounting for the phenotypes associated with maternal separation induced postnatal vocalizations.

Paternal social enrichment effects on maternal behavior and offspring growth.

Paternal environmental experiences are significant predictors of developmental outcomes in offspring and can occur even in the absence of paternal care. Although there has been a recent focus on the role of environmentally induced changes in the male germline in producing these effects, the potential mediating role of mothers has not been investigated. A role for mothers in the transmission of paternal effects has been well acknowledged in behavioral ecology, which predicts that females will dynamically adjust their reproductive investment in response to the qualities of their mate. In the present study, we show that a lifetime of socially enriched compared with impoverished housing conditions shifts anxiety-like behavior and gene expression of male mice. Females that mate with enriched-reared males exhibit increased levels of pup nursing and licking toward their offspring, which are associated with changes in gene expression within the maternal hypothalamus. Significantly, these changes in maternal behavior are correlated with the general levels of anxiety exhibited by their male mates. Further, we show that paternal environmental enrichment results in increased growth of their offspring. These results suggest that maternal-paternal interactions at mating may guide offspring development, with significant implications for the transgenerational transmission of paternal environmental experiences.

Is there a genomically imprinted social brain?

Imprinted genes (IGs) are expressed or silenced according to their parent-of-origin. These genes are known to play a role in regulating offspring growth, development and infant behaviors such as suckling and ultrasonic calls. In adults, neurally expressed IGs coordinate several behaviors including maternal care, sex, feeding, emotionality, and cognition. However, despite evidence from human psychiatric disorders and evolutionary theory that maternally and paternally expressed genes should also regulate social behavior, little empirical data from mouse research exists. This paper discusses data from a recent study (Garfield et al., 2011) that the IG Grb10 governs unique aspects of mouse social behavior and interprets the relevance of these findings for the future of this field.

Shaping the development of complex social behavior.

Early life experiences can have an enduring impact on the brain and behavior, with implications for stress reactivity, cognition, and social behavior. In particular, the neural systems that contribute to the expression of social behavior are altered by early life social environments. However, paradigms that have been used to alter the social environment during development have typically focused on exposure to stress, adversity, and deprivation of species-typical social stimulation. Here, we explore whether complex social environments can shape the development of complex social behavior. We describe lab-based paradigms for studying early life social complexity in rodents that are generally focused on enriching the social and sensory experiences of the neonatal and juvenile periods of development. The impact of these experiences on social behavior and neuroplasticity is highlighted. Finally, we discuss the degree to which our current approaches for studying social behavior outcomes give insight into "complex" social behavior and how social complexity can be better integrated into lab-based methodologies.

Sexual experience affects reproductive behavior and preoptic androgen receptors in male mice.

Reproductive behavior in male rodents is made up of anticipatory and consummatory elements which are regulated in the brain by sensory systems, reward circuits and hormone signaling. Gonadal steroids play a key role in the regulation of male sexual behavior via steroid receptors in the hypothalamus and preoptic area. Typical patterns of male reproductive behavior have been characterized, however these are not fixed but are modulated by adult experience. We assessed the effects of repeated sexual experience on male reproductive behavior of C57BL/6 mice; including measures of olfactory investigation of females, mounting, intromission and ejaculation. The effects of sexual experience on the number of cells expressing either androgen receptor (AR) or estrogen receptor alpha (ERα) in the primary brain nuclei regulating male sexual behavior was also measured. Sexually experienced male mice engaged in less sniffing of females before initiating sexual behavior and exhibited shorter latencies to mount and intromit, increased frequency of intromission, and increased duration of intromission relative to mounting. No changes in numbers of ERα-positive cells were observed, however sexually experienced males had increased numbers of AR-positive cells in the medial preoptic area (MPOA); the primary regulatory nucleus for male sexual behavior. These results indicate that sexual experience results in a qualitative change in male reproductive behavior in mice that is associated with increased testosterone sensitivity in the MPOA and that this nucleus may play a key integrative role in mediating the effects of sexual experience on male behavior.

The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies.

A century ago, foundational work by Thorleif Schjelderup-Ebbe described a 'pecking order' in chicken societies, where individuals could be ordered according to their ability to exert their influence over their group-mates. Now known as dominance hierarchies, these structures have been shown to influence a plethora of individual characteristics and outcomes, situating dominance research as a pillar of the study of modern social ecology and evolution. Here, we first review some of the major questions that have been answered about dominance hierarchies in the last 100 years. Next, we introduce the contributions to this theme issue and summarize how they provide ongoing insight in the epistemology, physiology and neurobiology, hierarchical structure, and dynamics of dominance. These contributions employ the full range of research approaches available to modern biologists. Cross-cutting themes emerging from these contributions include a focus on cognitive underpinnings of dominance, the application of network-analytical approaches, and the utility of experimental rank manipulations for revealing causal relationships. Reflection on the last 100 years of dominance research reveals how Schjelderup-Ebbe's early ideas and the subsequent research helped drive a shift from an essentialist view of species characteristics to the modern recognition of rich inter-individual variation in social, behavioural and physiological phenotypes. This article is part of the theme issue 'The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies'.

Neural systems that facilitate the representation of social rank.

Across species, animals organize into social dominance hierarchies that serve to decrease aggression and facilitate survival of the group. Neuroscientists have adopted several model organisms to study dominance hierarchies in the laboratory setting, including fish, reptiles, rodents and primates. We review recent literature across species that sheds light onto how the brain represents social rank to guide socially appropriate behaviour within a dominance hierarchy. First, we discuss how the brain responds to social status signals. Then, we discuss social approach and avoidance learning mechanisms that we propose could drive rank-appropriate behaviour. Lastly, we discuss how the brain represents memories of individuals (social memory) and how this may support the maintenance of unique individual relationships within a social group. This article is part of the theme issue 'The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies'.

DomArchive: a century of published dominance data.

Dominance behaviours have been collected for many groups of animals since 1922 and serve as a foundation for research on social behaviour and social structure. Despite a wealth of data from the last century of research on dominance hierarchies, these data are only rarely used for comparative insight. Here, we aim to facilitate comparative studies of the structure and function of dominance hierarchies by compiling published dominance interaction datasets from the last 100 years of work. This compiled archive includes 436 datasets from 190 studies of 367 unique groups (mean group size 13.8, s.d. = 13.4) of 135 different species, totalling over 243 000 interactions. These data are presented in an R package alongside relevant metadata and a tool for subsetting the archive based on biological or methodological criteria. In this paper, we explain how to use the archive, discuss potential limitations of the data, and reflect on best practices in publishing dominance data based on our experience in assembling this dataset. This archive will serve as an important resource for future comparative studies and will promote the development of general unifying theories of dominance in behavioural ecology that can be grounded in testing with empirical data. This article is part of the theme issue 'The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies'.

Epigenetics and the origins of paternal effects.

Though there are multiple routes through which parents can influence their offspring, recent studies of environmentally induced epigenetic variation have highlighted the role of non-genomic pathways. In addition to the experience-dependent modification of DNA methylation that can be achieved via mother-infant interactions, there has been increasing interest in the epigenetic mechanisms through which paternal influences on offspring development can be achieved. Epidemiological and laboratory studies suggest that paternal nutritional and toxicological exposures as well as paternal age and phenotypic variation can lead to variations in offspring and, in some cases, grand-offspring development. These findings suggest a potential epigenetic germline inheritance of paternal effects. However, it may be important to consider the interplay between maternal and paternal influences as well as the experimental dissociation between experience-dependent and germline transmission when exploring the role of epigenetic variation within the germline as a mediator of these effects. In this review, we will explore these issues, with a particular focus on the potential role of paternally induced maternal investment, highlight the literature illustrating the transgenerational impact of paternal experiences, and discuss the evidence supporting the role of epigenetic mechanisms in maintaining paternal effects both within and across generations.

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 individual's social status has not been thoroughly examined. In mice, cues about an individual's 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.

Stress in groups: Lessons from non-traditional rodent species and housing models.

A major feature of life in groups is that individuals experience social stressors of varying intensity and type. Social stress can have profound effects on health, social behavior, and ongoing relationships. Relationships can also buffer the experience of exogenous stressors. Social stress has most commonly been investigated in dyadic contexts in mice and rats that produce intense stress. Here we review findings from studies of diverse rodents and non-traditional group housing paradigms, focusing on laboratory studies of mice and rats housed in visible burrow systems, prairie and meadow voles, and mole-rats. We argue that the use of methods informed by the natural ecology of rodent species provides novel insights into the relationship between social stress, behavior and physiology. In particular, we describe how this ethologically inspired approach reveals how individuals vary in their experience of and response to social stress, and how ecological and social contexts impact the effects of stress. Social stress induces adaptive changes, as well as long-term disruptive effects on behavior and physiology.

A psychological intervention strengthens students' peer social networks and promotes persistence in STEM.

Retaining students in science, technology, engineering, and math (STEM) fields is critical as demand for STEM graduates increases. Whereas many approaches to improve persistence target individuals' internal beliefs, skills, and traits, the intervention in this experiment strengthened students' peer social networks to help them persevere. Students in a gateway biology course were randomly assigned to complete a control or values affirmation exercise, a psychological intervention hypothesized to have positive social effects. By the end of the term, affirmed students had an estimated 29% more friends in the course on average than controls. Affirmation also prompted structural changes in students' network positions such that affirmed students were more central in the overall course friendship network. These differing social trajectories predicted STEM persistence: Affirmed students were 11.7 percentage points more likely than controls to take the next course in the bioscience sequence, an effect that was statistically mediated by students' end-of-semester friendships.