The visible burrow system: A view from across the hall

Abstract

The visible burrow system (VBS) is an ethologically relevant social stress model that creates a distinct dominance hierarchy in rats. Randall Sakai’s laboratory performed an impressive series of studies documenting the very different impact of VBS exposure on the brain and behavior of dominants (DOM) and subordinates (SUBs). Hierarchy formation causes pronounced changes in metabolism in SUBs relative to both DOMs and unstressed controls, resulting in marked weight loss and metabolic imbalance. Stress testing revealed multiple phenotypes in the VBS, including DOMs, stress-responsive SUBs and stress-non-responsive SUBs. Stress-responsive SUBs have adrenal hypertrophy and elevated baseline corticosterone, consistent with prolonged HPA axis activation; however, peak acute stress responses are not sensitized. In contrast, stress non-responsive individuals do not mount a response to an acute stress, suggesting HPA axis hypofunction. In brain, SUBs exhibit a pattern of gene regulation consistent with impaired stress inhibition (e.g., hippocampal adrenocorticosteroid receptor down-regulation and dendritic retraction) and drive of stress pathways (e.g., increased locus coeruleus tyrosine hydroxylase expression). The non-responsive phenotype is distinguished by down-regulation of paraventricular nucleus corticotropin releasing hormone expression and enhanced neuropeptide Y expression in amygdala. The brain ‘signature’ created by VBS hierarchy formation differed substantially from that of another well-studied chronic stress model (chronic variable stress). Thus, the impact of VBS is mediated by neurocircuit mechanisms at least in part distinct that of other chronic stress modalities, and suggests that the nature of the stressor may be an essential consideration in development of treatment strategies for stress-related diseases.

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

“…Further, relative to dominants, subordinate males generally show elevated baseline corticosterone and adrenal hypertrophy coupled with reduced levels of corticotropin binding globulin (CBG) indicating higher levels of free corticosterone (Spencer et al, 1996), thymic atrophy and reduced body weights (McEwen et al, 2015;Tamashiro et al, 2005). These physiological outcomes are consistent with other chronic stress exposures such as chronic variable stress (CVS) (Herman and Tamashiro, 2017;McEwen et al, 2015). However, it should be noted that these differences are not found in all VBS studies, suggesting that social contexts between VBS colonies may vary and influence physiological outcomes (Buwalda et al, 2017;Dijkstra et al, 1992;Kozorovitskiy and Gould, 2004;McEwen et al, 2015).…”

“…Unlike several stress paradigms that emphasize controlled exposures to known stressors (e.g. restraint stress, chronic variable stress, social defeat stress) (Herman and Tamashiro, 2017), clearly the social stress exposure from living in VBS is not equivalent for all individuals. Depending upon the social context (e.g.…”

Rodent models of social stress and neuronal plasticity: Relevance to depressive-like disorders

“…1B), where victims are housed in continuous close, visual and olfactory contact with neighboring attackers which makes this more a chronic social stress model with a dominant and a subordinate animal [35,36]. The third variant is also making use of hierarchical dominance contexts where chronic social stress of subordination is studied in hierarchical colony structures such as the visible burrow system [37][38][39] (Fig. 1C).…”

“…Multiple factors may be causal in volumetric changes such as structural remodeling, neuro-and gliogenesis and apoptosis [29,63,64]. Social stress paradigms such as psychosocial stress in the resident-intruder paradigm and chronic stress of subordination in the visible burrow system in several animal models showed dendritic atrophy in CA1 and CA3 pyramidal neurons that persisted even after prolonged stress free recovery periods [39,41,65,66]. Somewhat surprisingly, dendritic atrophy in CA3 neurons was not only observed in animals exposed to chronic social stress but also observed in rats that were socially dominant in social colony structures like the visible burrow system [65] which may indicate that maintaining social dominance can be a source of chronic social stress.…”

Analytic and Interpretational Pitfalls to Measuring Fecal Corticosterone Metabolites in Laboratory Rats and Mice

“…58,81 The variation in body weight and HPA status among mixedsex group-housed rats in visible burrow systems shows that individual animals respond differently in a social situation depending on their social status and that the animals in the group can become to some extent physiologically distinct. 10,11,32 This basic conclusion has been corroborated in several studies of commonly-used laboratory strains of rats or mice in studies comparing individual and group housing: glucocorticoid levels are either the same or lower in singly housed animals, 7,33,35,42,45 despite some differences related to strains and housing density. 63,89 One study showed that after separation of group-housed female mice, the concentration of FCM decreased from day 1 to day 3 after separation and stabilized at these lower concentrations during days 4 to 7, suggesting an adaptation to individual housing that was associated with lower HPA reactivity.…”