br Amygdala involvement in social behavior throughout the li

Amygdala involvement in social behavior throughout the lifespan In humans, the amygdala is implicated in social behavior in adults (Thomas et al., 2001), as well as during development (Skuse et al., 2003; Tottenham and Sheridan, 2009). Furthermore, research has shown that humans with disorders associated with social behavior deficits, such as Autism and Williams Syndrome, show amygdala abnormalities (Baron-Cohen et al., 2000; Bachevalier et al., 2000; Critchley et al., 2000; Howard et al., 2000; Pierce et al., 2001; Haas et al., 2009; Paul et al., 2009). Moreover, studies in nonhuman ace inhibitor demonstrate that adult monkeys without amygdalae display inappropriate social behavior (Amaral, 2003; Baron-Cohen et al., 2000; Bliss-Moreau et al., 2011; Brothers et al., 1990; Emery et al., 2001; Malkova et al., 2010). While the amygdala is also implicated in social behavior in children (Tottenham and Sheridan, 2009), its role is less clear. Studies on abused and neglected children, as well as children with PTSD, indicates changes in the response to threatening faces (Pine et al., 2005; Pollak et al., 2000). The most dramatic developmental differences were first observed in non-human primates, where infant amygdala lesions lead to decreased fear response to normally threatening stimuli and an enhanced response to novel social situations (Amaral, 2002, 2003). This parallels work showing impaired threat assessment in abused rats with amygdala dysfunction (Perry, Santiago, & Sullivan, in press) and rats that were stressed during peripuberty (Marquez et al., 2013). The rodent literature allows for more precise manipulations of specific amygdala nuclei. Social behavior in adult rodents appears to rely on the medial amygdala (Rasia-Filho et al., 2000). It has been shown that c-Fos expression, an indirect marker of neural activation, increases in the medial amygdala following social encounters and maternal behavior in rodent models (Fleming et al., 1994; Kirkpatrick et al., 1994). Medial amygdala activation is also associated with rodent parental behavior, which is blocked by lesioning this nucleus (Ferguson et al., 2002; Gobrogge et al., 2007; Kirkpatrick et al., 1994). While the medial amygdala has a prominent role in social behavior, the basolateral, central and cortical amygdala nuclei have also been implicated (Katayama et al., 2009). As will be discussed below, these nuclei form part of a functional circuit with the hippocampus and vmPFC that is critically engaged in complex forms of social behavior.
Implications for complex social behavior Aberrant processing of social and threatening cues stemming from amygdala dysfunction is a hallmark of psychiatric sequelae following early-life abuse and neglect (Levin et al., 2015; Teicher et al., 2003; Troller-Renfree et al., 2016; Zeanah and Gleason, 2015). As individuals mature, increasingly complex social demands may multiply the consequences of impaired social behavior, amplifying stress and even compromising welfare. Exploring these complex social arrangements in animal models can provide insight into the mechanisms underlying long-term effects of social deficits and identify therapeutic targets for attachment trauma in early life. Dominance hierarchies provide one example of a complex social arrangement determined by individual differences that can result from early life experience. In the wild, rats are among a wide variety of species that naturally form dominance hierarchies as a result of competition for limited resources (Sapolsky, 2005). This can be simulated in the laboratory using a visible burrow system, a semi-naturalistic enclosure that replicates many of the challenges and opportunities of group-living in nature; in this setting, rats rapidly form stable dominance hierarchies (Fig. 3) (Blanchard et al., 1995, 1988; Opendak et al., 2016). A rich literature has described the effects of life in a dominance hierarchy on its members, including measures of behavior, hormones and physiology (Blanchard et al., 1995; Hardy et al., 2002). These studies have focused on differences between dominants and subordinates within the aggressive Long Evans (LE) rat strain. The factors that contribute to social position are complex, but the consequences of stratification can be dramatic for an animal’s quality of life. When LE rats form a dominance hierarchy within a laboratory enclosure, it has been shown that subordinate rats have elevated levels of CORT compared to dominants and can be prone to illness and weight loss due to chronic stress (Blanchard et al., 1995; Hardy et al., 2002). Subordinate rats show a decrease in overall activity and social behaviors, including aggression and sexual advances. In addition, they show an increase in a range of defensive responses to the dominant male (Blanchard et al., 1995, 2001). Furthermore, subordinates exhibit increases in the relative sizes of adrenal glands and spleen and decreases in the sizes of the thymus and testes than dominants. In contrast, dominants enjoy preferential access to resources, as well as increases in markers of adult-brain plasticity. Specifically, dominant rats show enhanced adult neurogenesis in the ventral dentate gyrus of the hippocampal formation, an effect that also has been shown in baboons (Kozorovitskiy and Gould, 2004; Peragine et al., 2014; Wu et al., 2014).