Early experience alters developmental trajectory of central oxytocin systems involved in hypothalamic-pituitary-adrenal axis regulation in Long-Evans rats.

Oxytocin is important for postnatal developmental experiences for mothers, infants, and transactions between them. Oxytocin is also implicated in adult affiliative behaviors, including social buffering of stress. There is evidence for connections between early life experience and adult oxytocin system functioning, but effects of early experience on behavioral, endocrine, and neurophysiological outcomes related to adult social buffering are not well explored. We use a limited bedding and nesting (LBN) material paradigm as an environmental disruption of early experiences and assessed central oxytocin systems in brain regions related to hypothalamic-pituitary-adrenal (HPA) axis regulation (paraventricular nucleus of the hypothalamus, amygdala, hippocampus). We also assessed developmentally-appropriate social behaviors and HPA reactivity during social buffering testing in adulthood. LBN litters had larger huddles and more pups visible compared to control litters during the first two weeks of life. LBN also altered the developmental trajectory of oxytocin-expressing cells and oxytocin receptor cells, with increases in oxytocin receptor cells at P15 in LBN pups. By adulthood, LBN females had more and LBN males had fewer oxytocin and oxytocin receptor cells in these areas compared to sex-matched controls. Adult LBN females, but not LBN males, had behavioral changes during social interaction and social buffering testing. The sex-specific effects of early experience on central oxytocin systems and social behavior may contribute to female resilience to early life adversity.

Uncovering sources of maternal variability: Inherited and environmental contributions to maternal phenotype.

Intergenerational patterns of parental behavior, especially maternal behavior, have been observed across mammalian species including humans, non-human primates, and rodents. These patterns are largely experience-dependent as opposed to genetically induced, with experiences in early-life serving an essential role in directing maternal behavior expressed later in life. Environmental conditions can also alter maternal behavior with consequences for offspring neurodevelopment and interactions with the next generation. Here, we describe effects of lineage during developmental environmental disruption using a limited bedding and nesting material manipulation during the first 2 weeks of life. Dams from three lineages were placed in environments containing either abundant nesting material or reduced nesting material. Environmental condition affected eight measures of maternal behavior and dam lineage affected 12 measures of maternal behavior during the first two postnatal weeks. Lineage, condition, and pup sex predicted pup body weight immediately following the manipulation, with lineage accounting for the largest portion of variance in body weight. Although from a limited sample, these data are the first to examine effects of lineage and environment simultaneously and suggest dam lineage may be a better predictor of maternal behavior than current environmental conditions with important implications for pup outcomes.

Limited bedding and nesting material changes indices of cellular metabolism and behavioral thermal regulation in Long-Evans rats during the first two weeks of life.

A quality nest can buffer pups from the cold climate in typical laboratory housing by insulating them from cool ambient air and facilitating pup huddling during early life when many thermal regulation strategies are not yet developed. The limited nesting material (LBN) manipulation prevents the dam from constructing a quality nest. In the present study, we investigate whether LBN presents a thermal challenge to pups across the first two postnatal weeks. Behavioral thermal regulation (huddling), physiological thermogenesis (activation of brown adipose tissue; BAT), changes in cellular metabolism (mitochondrial biogenesis) in peripheral and central tissues, and maternal behavior were measured in environments with LBN or abundant bedding on postnatal day (P) 2, P6, P10, and P14. The huddle of LBN litters had greater area, greater perimeter, and reduced circularity, and more pups visible. Control male pups were visible longer than control female pups during home cage recordings and LBN pups were visible longer than control pups. Heart weight relative to body weight was higher in LBN pups after P2. LBN affected BAT, but not white adipose tissue (WAT), activation in a sex and age-specific manner, with reductions in UCP1 expression after P2. Pups appear especially affected by LBN on P6, when mitochondrial DNA copy number was reduced in WAT. Mitochondrial DNA copy number was reduced in LBN pups in the hippocampus but not the brainstem. Our data provide evidence of changes in indices of thermal regulation and cellular metabolism in LBN pups which may be indicative of changes in energy allocation during development.

Toxic stress history and hypothalamic-pituitary-adrenal axis function in a social stress task: Genetic and epigenetic factors.

Histories of early life stress (ELS) or social discrimination can reach levels of severity characterized as toxic to mental and physical health. Such toxic social stress during development has been linked to altered acute hypothalamic-pituitary-adrenal (HPA) response to social stress in adulthood. However, there are important individual differences in the size and direction of these effects. We explored developmental, genetic, epigenetic, and contextual sources of individual differences in the relationship between ELS, discrimination, and adult responses to acute social stress in a standard laboratory test. Additional measures included perceived status, social support, background activity of HPA axis, and genetic variants in aspects of the stress response system. Participants (n = 90) answered questions about historical and ongoing stress, provided a DNA sample to examine genetic polymorphisms and epigenetic marks, and underwent the Trier Social Stress Test (TSST) during which three saliva samples were collected to assess HPA function. Individuals who reported high levels of childhood adversity had a blunted salivary cortisol response to the TSST. Childhood adversity, discrimination experiences, and FKBP5 genotype were found to predict pretest cortisol levels. Following up on recent observations that the glucocorticoid receptor directly interacts with the mitochondrial genome, particularly the NADH dehydrogenase 6 (MT-ND6) gene, individuals who reported high childhood adversity were also found to have higher percent methylation across six CpG sites upstream of MT-ND6. These findings suggest multiple contributions across psychological, genetic, epigenetic, and social domains to vulnerability and resilience in hypothalamic-pituitary-adrenal axis regulation. Further study to examine how these multiple contributors affect developmental endpoints through integrated or independent pathways will be of use.

Hair cortisol and lifetime discrimination: Moderation by subjective social status.

Discrimination has been associated with elevated cortisol as measured in saliva, blood, and urine. This study investigated the association between lifetime discrimination and hair cortisol concentrations, considered a measure of chronic stress. We recruited 180 young adults from diverse backgrounds. Participant responses to lifetime discrimination, home stress, and subjective status measures were recorded. Lifetime discrimination significantly predicted hair cortisol concentrations, supporting past research that discrimination experiences impact neuroendocrine systems. To our knowledge, these are the first findings associating hair cortisol concentrations with discrimination and supports prior evidence positing discrimination as a chronic stressor that serves as a risk factor for chronic disease.

Maternal behavior, infant development, and the question of developmental resources.

The natural development of maternal and infant behavior occurs in a dyad characterized by synchrony and reciprocal interactions. Major concepts used to describe and analyze this synchrony were reviewed. It was concluded that the dyad undergoes a developmental progression in which each part of the dyad is both a developing organism and a reliably changing milieu forming part of the extended inheritance of the other. The reliability of inherited resources is rooted in interactions essential to life, such as those used to transfer metabolic needs to dependent offspring; to stimulation (incidentally but necessarily) associated with life-supporting mechanisms; and to perceptual, motor, or learning mechanisms used to extract specific resources from the available milieu. The diverse resources in extended inheritance contribute to the construction of new traits through opportunistic shaping or regulating interactions among them that are unrestricted by their function at earlier stages.

Can behavioral evolution be measured on a staircase? A commentary.

The serious, comparative study of behavioral complexity that Greenberg et al. advocate is a progressive direction for the field, but their proposal to separate comparative psychology from its roots in evolutionary biology seems regressive. Modern evolutionary theory has been broadened within biology to include development and paleontology alongside natural selection, making closer integration with that discipline particularly timely. Such an integrated evolutionary approach in psychology would offer a useful alternative to the adaptationism popularized by evolutionary psychology. Although the differences between comparative psychologists and biologists may be blurred in the process, the behavioral sciences will be better served by a rich biological approach to evolution than by a uniquely psychological approach.