Sex-Specific Mechanism of Social Hierarchy in Mice

Abstract

The establishment of social hierarchies is a naturally occurring, evolutionarily conserved phenomenon with a well-established impact on fitness and health. Investigations of complex social group dynamics may offer novel opportunities for translational studies of autism spectrum disorder. Here we describe a robust behavioral paradigm using an automated version of the tube test. Isogenic groups of male and female mice establish linear social hierarchies that remain highly stable for at least 14 days, the longest interval tested. Remarkably, however, their social strategy is sex-specific: females primarily utilize intrinsic attributes, whereas males are strongly influenced by prior social experience. Using both genetic and pharmacological manipulations, we identify testosterone as a critical sex-specific factor for determining which social strategy is used. Males inheriting a null mutation of the sex-determining region Y (Sry) gene used a similar social cognitive strategy as females. In contrast, females with transgenic expression of Sry utilized a typically male social strategy. Analogously, castration of males and testosterone supplementation of females yielded similar outcomes, with a reversal of their social cognitive strategy. Together, our results demonstrate a sex-specific mechanism underlying social hierarchy, in which both males and females retain the functional capacity to adapt their social strategy. More generally, we expect the automated tube test to provide an important complementary approach for both fundamental and translational studies of social behavior.

Temporal dynamics of social hierarchy formation and maintenance in male mice

“…personality variables like risk taking or boldness, or social competence) may be just as important as or more important than aggression in determining social status in mice (David, Auclair, & C ezilly, 2011;Fox, Ladage, Roth, & IIPravosudov, 2009;Hsu, Earley, & Wolf, 2006;Taborsky & Oliveira, 2012). Second, this finding suggests that standard laboratory tests of social dominance using animals tested in pairs in tasks such as the tube-test (van den Berg et al, 2015;Wang et al, 2011), food competition (Benner et al, 2014;de Jong, Korosi, Harris, Perea-Rodriguez, & Saltzman, 2012;Timmer, Cordero, Sevelinges, & Sandi, 2011) or aggression (Bales & Carter, 2003;Branchi et al, 2013) tests, are not necessarily robust indicators of an individual's ability to ascend a social hierarchy when living within a large social group comprising a number of complex social relationships.…”

“…Although these tests reveal behaviour characteristics of individual mice and the relationship between two individuals at a given point in time, they do not provide information about how relationships develop over time or how relationships are adjusted within a large social network. Dominance in pairs of mice is usually assessed with dyadic tubetests (van den Berg, Lamballais, & Kushner, 2015;Curley, 2011;Wang et al, 2011), food, sex or other reward competition tests (Benner, Endo, Endo, Kakeyama, & Tohyama, 2014;Jupp et al, 2015;Nelson, Cunningham, Ruff, & Potts, 2015) and aggression tests (Branchi et al, 2013;Ginsburg & Allee, 1942). Problematically, results in these social contexts do not necessarily relate to overall social dominance within a larger group context where relationships are embedded (Chase, 1982b).…”

Fragile X mice have robust mGluR5-dependent alterations of social behaviour in the Automated Tube Test

“…Fragile X syndrome (FXS) is a monogenic developmental disorder with a prevalence of 1 in 4000 males and 1 in 6000 females (Turner et al, 1996). The complex neurological phenotype observed in FXS results from a lack of fragile X mental retardation protein (FMRP) beginning in early development (Oostra and Willemsen, 2003).…”

Of Mice and Men: Empirical Support for the Population-Based Social Epistasis Amplification Model (a Comment on )

“…Certain cultural changes, such as secularization, have also been connected to fertility decline at the group and individual levels (Meisenberg, 2011), and there is evidence that irreligiosity is associated with behavioral and physical abnormalities indicative of higher relative burdens of deleterious mutations (Dutton, 2017). Religion is a group-level adaptation in humans (Wilson, 2002), as is social hierarchy in mice (van den Berg et al, 2015). Thus, the carriers of spiteful mutations may disrupt the patterns of social epistasis that sustain religiosity and other group-level adaptations, and consequently lower fitness.…”