Social status mediated variation in hypothalamic transcriptional profiles of male mice.

Animals of different social status exhibit variation in aggression, territorial and reproductive behavior as well as activity patterns, feeding, drinking and status signaling. This behavioral and physiological plasticity is coordinated by underlying changes in brain gene transcription. Using Tag-based RNA sequencing (Tag-seq), we explore RNA transcriptomes from the medial preoptic area (mPOA) and ventral hypothalamus (vHYP) of male mice of different social ranks in a dominance hierarchy and detect candidate genes and cellular pathways that underlie status-related plasticity. Within the mPOA, oxytocin (Oxt) and vasopressin (Avp) are more highly expressed in subdominant mice compared to other ranks, while nitric oxide synthase (Nos1) has lower expression in subdominant mice. Within the vHYP, we find that both orexigenic and anorexigenic genes involved in feeding behavior, including agouti-related peptide (Agrp), neuropeptide-Y (Npy), galanin (Gal), proopiomelanocortin (Pomc), and Cocaine- and Amphetamine-Regulated Transcript Protein prepropeptide (Cartpt), are less expressed in dominant animals compared to more subordinate ranks. We suggest that this may represent a reshaping of feeding circuits in dominant compared to subdominant and subordinate animals. Furthermore, we determine several genes that are positively and negatively associated with the level of despotism (aggression) in dominant males. Ultimately, we identify hypothalamic genes controlling feeding and social behaviors that are differentially transcribed across animals of varying social status. These changes in brain transcriptomics likely support phenotypic variation that enable animals to adapt to their current social status.

Postnatal maternal care predicts divergent weaning strategies and the development of social behavior.

Maternal care experienced during postnatal development predicts long-term neurobiological and behavioral outcomes. However, the cascade of behavioral changes that emerge in response to maternal care has not been elucidated. In the current study, we examine naturally occurring variation in postnatal licking/grooming (LG) in C57BL/6J mice to determine its impact on preweaning maternal and pup behavior, the weaning process, the pace of developmental change, the emergence of social behavior, and indices of anxiety-like behavior in adulthood. Our analyses indicate that lower postnatal LG is associated with truncated and more infrequent maternal behavior during the preweaning period. Moreover, compared to High LG dams, Low LG dams are observed to actively wean their offspring sooner and have offspring that play more frequently. The heightened pace of developmental change observed in offspring of Low LG dams suggests a more rapid transition to behavioral and nutritional independence, which could have implications for future reproductive strategies.

The evolution of genomic imprinting: theories, predictions and empirical tests.

The epigenetic phenomenon of genomic imprinting has motivated the development of numerous theories for its evolutionary origins and genomic distribution. In this review, we examine the three theories that have best withstood theoretical and empirical scrutiny. These are: Haig and colleagues' kinship theory; Day and Bonduriansky's sexual antagonism theory; and Wolf and Hager's maternal-offspring coadaptation theory. These theories have fundamentally different perspectives on the adaptive significance of imprinting. The kinship theory views imprinting as a mechanism to change gene dosage, with imprinting evolving because of the differential effect that gene dosage has on the fitness of matrilineal and patrilineal relatives. The sexual antagonism and maternal-offspring coadaptation theories view genomic imprinting as a mechanism to modify the resemblance of an individual to its two parents, with imprinting evolving to increase the probability of expressing the fitter of the two alleles at a locus. In an effort to stimulate further empirical work on the topic, we carefully detail the logic and assumptions of all three theories, clarify the specific predictions of each and suggest tests to discriminate between these alternative theories for why particular genes are imprinted.

Variation in maternal and anxiety-like behavior associated with discrete patterns of oxytocin and vasopressin 1a receptor density in the lateral septum.

The relationship between anxiety and maternal behavior has been explored across species using a variety of approaches, yet there is no clear consensus on the nature or direction of this relationship. In the current study, we have assessed stable individual differences in anxiety-like behavior in a large cohort (n=57) of female F2 hybrid mice. Using open-field behavior as a continuous and categorical (high vs. low) measure we examined the relationship between the anxiety-like behavior of virgin F2 females and the subsequent maternal behavior of these females. In addition, we quantified oxytocin (OTR) and vasopressin (V1a) receptor density within the lateral septum to determine the possible correlation with anxiety-like and maternal behavior. We find that, though activity levels within the open-field do predict latency to engage in pup retrieval, anxiety-like measures on this test are otherwise not associated with subsequent maternal behavior. OTR density in the dorsal lateral septum was found to be negatively correlated with activity levels in the open-field and positively correlated with frequency of nursing behavior. V1a receptor density was significantly correlated with postpartum licking/grooming of pups. Though we do not find support for the hypothesis that individual differences in trait anxiety predict variation in maternal behavior, we do find evidence for the role of OTR and V1a receptors in predicting maternal behavior in mice and suggest possible methodological issues (such as distinguishing between trait and state anxiety) that will be a critical consideration for subsequent studies of the anxiety-maternal behavior relationship. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

Behavioural and physiological plasticity in social hierarchies.

Individuals occupying dominant and subordinate positions in social hierarchies exhibit divergent behaviours, physiology and neural functioning. Dominant animals express higher levels of dominance behaviours such as aggression, territorial defence and mate-guarding. Dominants also signal their status via auditory, visual or chemical cues. Moreover, dominant animals typically increase reproductive behaviours and show enhanced spatial and social cognition as well as elevated arousal. These biobehavioural changes increase energetic demands that are met via shifting both energy intake and metabolism and are supported by coordinated changes in physiological systems including the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes as well as altered gene expression and sensitivity of neural circuits that regulate these behaviours. Conversely, subordinate animals inhibit dominance and often reproductive behaviours and exhibit physiological changes adapted to socially stressful contexts. Phenotypic changes in both dominant and subordinate individuals may be beneficial in the short-term but lead to long-term challenges to health. Further, rapid changes in social ranks occur as dominant animals socially ascend or descend and are associated with dynamic modulations in the brain and periphery. In this paper, we provide a broad overview of how behavioural and phenotypic changes associated with social dominance and subordination are expressed in neural and physiological plasticity. 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'.

Developmental shifts in the behavioral phenotypes of inbred mice: the role of postnatal and juvenile social experiences.

The interaction between genotype and environment is an important feature of the process of development. We investigate this interaction by examining the influence of postnatal cross-fostering and post-weaning cross-housing on the behavioral development of 129S and B6 mice. Following cross-fostering, we found significant alterations in the frequency of maternal care as a function of maternal strain and pup type as well as interactions between these variables. In adulthood, we find there are sex-specific and strain-specific alterations in anxiety-like behavior as a function of rearing environment, with males exhibiting more pronounced rearing-induced effects. Mixed-strain housing of weanlings was found to lead to alterations in home-cage social and feeding behavior as well as changes in adult anxiety-like responses of 129S mice. Anxiety-like behavior in B6 mice was altered as a function of the interaction between housing condition and weaning weight. These data illustrate the complex pathways through which early and later social experiences may lead to variations in behavior.

Parent-of-origin and trans-generational germline influences on behavioral development: the interacting roles of mothers, fathers, and grandparents.

Mothers and fathers do not contribute equally to the development of their offspring. In addition to the differential investment of mothers versus fathers in the rearing of offspring, there are also a number of germline factors that are transmitted unequally from one parent or the other that contribute significantly to offspring development. This article shall review four major sources of such parent-of-origin effects. Firstly, there is increasing evidence that genes inherited on the sex chromosomes including the nonpseudoautosomal part of the Y chromosome that is only inherited from fathers to sons, contribute to brain development and behavior independently of the organizing effects of sex hormones. Secondly, recent work has demonstrated that mitochondrial DNA that is primarily inherited only from mothers may play a much greater than anticipated role in neurobehavioral development. Thirdly, there exists a class of genes known as imprinted genes that are epigenetically silenced when passed on in a parent-of-origin specific manner and have been shown to regulate brain development and a variety of behaviors. Finally, there is converging evidence from several disciplines that environmental variations experienced by mothers and fathers may lead to plasticity in the development and behavior of offspring and that this phenotypic inheritance can be solely transmitted through the germline. Mechanistically, this may be achieved through altered programming within germ cells of the epigenetic status of particular genes such as retrotransposons and imprinted genes or potentially through altered expression of RNAs within gametes.

Increased body fat in mice with a targeted mutation of the paternally expressed imprinted gene Peg3.

Peg3 encodes a C2H2 type zinc finger protein that is implicated in a novel physiological pathway regulating core body temperature, feeding behavior, and obesity in mice. Peg3+/- mutant mice develop an excess of abdominal, subcutaneous, and intra-scapular fat, despite a lifetime of lower food intake than wild-type animals. However, they start life with reduced fat reserves and are slower to enter puberty. These mice maintain a lower core body temperature, fail to respond to a cold challenge, and have lower metabolic activity as measured by oxygen consumption. Plasma leptin levels are significantly higher than in wild types, and Peg3+/- mice appear to have developed leptin resistance. Administration of exogenous leptin resulted in a significant reduction in food intake in wild-type mice that was not observed in Peg3+/- mutants. This mutation, which is strongly expressed in hypothalamic tissue during development, has the capacity to regulate multiple events relating to energy homeostasis.

Social influences on neurobiology and behavior: epigenetic effects during development.

The quality of the social environment can have profound influences on the development and activity of neural systems with implications for numerous behavioral and physiological responses, including the expression of emotionality. Though social experiences occurring early in development may be particularly influential on the developing brain, there is continued plasticity within these neural circuits amongst juveniles and into early adulthood. In this review, we explore the evidence derived from studies in rodents which illustrates the social modulation during development of neural systems, with a particular emphasis on those systems in which a long-term effect is observed. One possible explanation for the persistence of dynamic changes in these systems in response to the environment is the involvement of epigenetic mechanisms, and here we discuss recent studies which support the role of these mechanisms in mediating the link between social experiences, gene expression, neurobiological changes, and behavioral variation. This literature raises critical questions about the interaction between neural systems, the concordance between neural and behavioral changes, sexual dimorphism in effects, the importance of considering individual differences in response to the social environment, and the potential of an epigenetic perspective in advancing our understanding of the pathways leading to variations in mental health.

Mother-infant bonding and the evolution of mammalian social relationships.

A wide variety of maternal, social and sexual bonding strategies have been described across mammalian species, including humans. Many of the neural and hormonal mechanisms that underpin the formation and maintenance of these bonds demonstrate a considerable degree of evolutionary conservation across a representative range of these species. However, there is also a considerable degree of diversity in both the way these mechanisms are activated and in the behavioural responses that result. In the majority of small-brained mammals (including rodents), the formation of a maternal or partner preference bond requires individual recognition by olfactory cues, activation of neural mechanisms concerned with social reward by these cues and gender-specific hormonal priming for behavioural output. With the evolutionary increase of neocortex seen in monkeys and apes, there has been a corresponding increase in the complexity of social relationships and bonding strategies together with a significant redundancy in hormonal priming for motivated behaviour. Olfactory recognition and olfactory inputs to areas of the brain concerned with social reward are downregulated and recognition is based on integration of multimodal sensory cues requiring an expanded neocortex, particularly the association cortex. This emancipation from olfactory and hormonal determinants of bonding has been succeeded by the increased importance of social learning that is necessitated by living in a complex social world and, especially in humans, a world that is dominated by cultural inheritance.