Limited Bedding and Nesting as a Model for Early-Life Adversity in Mice.

Early-life adversity (ELA), such as abuse, neglect, lack of resources, and an unpredictable home environment, is a known risk factor for developing neuropsychiatric disorders such as depression. Animal models for ELA have been used to study the impact of chronic stress on brain development, and typically rely on manipulating the quality and/or quantity of maternal care, as this is the major source of early-life experiences in mammals, including humans. Here, a detailed protocol for employing the Limited Bedding and Nesting (LBN) model in mice is provided. This model mimics a low-resource environment, which provokes fragmented and unpredictable patterns of maternal care during a critical developmental window (postnatal days 2-9) by limiting the amount of nesting materials given to the dam to build a nest for her pups and separating the mice from the bedding via a mesh platform in the cage. Representative data are provided to illustrate the changes in maternal behavior, as well as the diminished pup weights and long-term changes in basal corticosterone levels, that result from the LBN model. As adults, offspring reared in the LBN environment have been shown to exhibit an aberrant stress response, cognitive deficits, and anhedonia-like behavior. Therefore, this model is an important tool to define how the maturation of stress-sensitive brain circuits is altered by ELA and results in long-term behavioral changes that confer vulnerability to mental disorders.

Sex-specific behavioral outcomes of early-life adversity and emerging microglia-dependent mechanisms.

Early-life adversity (ELA) is known to alter brain circuit maturation as well as increase vulnerability to cognitive and emotional disorders. However, the importance of examining sex as a biological variable when researching the effects of ELA has not been considered until recently. This perspective discusses the sex-specific behavioral outcomes of ELA in both humans and animal models, then proposes microglia-mediated mechanisms as a potential underlying cause. Recent work in rodent models suggests that ELA provokes cognitive deficits, anhedonia, and alcohol abuse primarily in males, whereas females exhibit greater risk-taking and opioid addiction-related behaviors. In addition, emerging evidence identifies microglia as a key target of ELA. For example, we have recently shown that ELA inhibits microglial synapse engulfment and process dynamics in male mice, leading to an increase in excitatory synapse number onto corticotrophin-releasing hormone (CRH)-expressing neurons in the paraventricular nucleus of the hypothalamus (PVN) and aberrant stress responses later in life. However, ELA-induced synaptic rewiring of neural circuits differs in females during development, resulting in divergent behavioral outcomes. Thus, examining the role of microglia in the sex-specific mechanisms underlying ELA-induced neuropsychiatric disorders is an important topic for future research.

Behavioral trajectories of aging prairie voles (Microtus ochrogaster): Adapting behavior to social context wanes with advanced age.

Several studies using mice have examined the effects of aging on cognitive tasks, as well as sensory and motor functions. However, few studies have examined the influence of aging on social behavior. Prairie voles (Microtus ochrogaster) are a socially monogamous and biparental rodent that live in small family groups and are now among the most popular rodent models for studies examining social behavior. Although the social behavioral trajectories of early-life development in prairie voles have been well-studied, how social behavior may change throughout adulthood remains unknown. Here we examined behavior in virgin male and female prairie voles in four different age groups: postnatal day (PND) 60-80, 140-160, 220-240, and 300-320. All animals underwent testing in a novel object task, a dominance test, a resident-intruder test, and several iterations of social approach and social interaction tests with varying types of social stimuli (i.e., novel same-sex conspecific, novel opposite-sex conspecific, familiar same-sex sibling/cagemate, small group of novel same-sex conspecifics). We found that age influenced neophobia and dominance, but not social approach behavior. Further, we found that young adult, but not older adult, prairie voles adapt prosocial and aggressive behavior relative to social context, and that selective aggression occurs in relation to age even in the absence of a pair bond. Our results suggest that prairie voles calibrate social phenotype in a context-dependent manner in young adulthood and stop adjusting behavior to social context in advanced age, demonstrating that social behavior is plastic not only throughout early development, but also well into adulthood. Together, this study provides insight into age-related changes in social behavior in prairie voles and shows that prairie voles may be a viable model for studying the cognitive and physiological benefits of social relationships and social engagement in advanced age.