A novel escapable social interaction test reveals that social behavior and mPFC activation during an escapable social encounter are altered by post-weaning social isolation and are dependent on the aggressiveness of the stimulus rat

Abstract

Post-weaning social isolation (PSI) has been shown to increase aggressive behavior and alter medial prefrontal cortex (mPFC) function in social species such as rats. Here we developed a novel escapable social interaction test (ESIT) allowing for the quantification of escape and social behaviors in addition to mPFC activation in response to an aggressive or nonaggressive stimulus rat. Male rats were exposed to 3 weeks of PSI (ISO) or group (GRP) housing, and exposed to 3 trials, with either no trial, all trials, or the last trial only with a stimulus rat. Analysis of social behaviors indicated that ISO rats spent less time in the escape chamber and more time engaged in social interaction, aggressive grooming, and boxing than did GRP rats. Interestingly, during the third trial all rats engaged in more of the quantified social behaviors and spent less time escaping in response to aggressive but not nonaggressive stimulus rats. Rats exposed to nonaggressive stimulus rats on the third trial had greater c-fos and ARC immunoreactivity in the mPFC than those exposed to an aggressive stimulus rat. Conversely, a social encounter produced an increase in large PSD-95 punctae in the mPFC independently of trial number, but only in ISO rats exposed to an aggressive stimulus rat. The results presented here demonstrate that PSI increases interaction time and aggressive behaviors during escapable social interaction, and that the aggressiveness of the stimulus rat in a social encounter is an important component of behavioral and neural outcomes for both isolation and group-reared rats.

Roles of Medial Prefrontal Cortex Activity in Human and Animal Social Learning

“…Additional studies demonstrating social learning processes in the mPFC involve self-reflection, person perception, and theory of mind/mentalizing (Amodio and Frith 2006), understanding self and others, decision making in adults (Heekeren et al 2008), predicting others' preferences (Kang et al 2013), and learning and predicting the likely outcomes of actions of the self and others (Alexander and Brown 2011). Additionally, it has been demonstrated that the mPFC is implicated in facilitating coordination between animals, regulating social interactions, and carrying out complex defensive behaviors (Goodell et al 2017).…”

“…Recent evidence highlights the mPFC's direct involvement in regulating aggressive behaviors. According to Goodell et al (2017), aggression observed in rodents may be directly associated with changes in mPFC function due to postweaning social isolation (PSI) may be directly related to aggression in rodents that were previously exposed to PSI. Intuitively this would make sense, as emotion regulation and executive functioning are both strongly related to mPFC functionality (Goodell et al 2017).…”

“…According to Goodell et al (2017), aggression observed in rodents may be directly associated with changes in mPFC function due to postweaning social isolation (PSI) may be directly related to aggression in rodents that were previously exposed to PSI. Intuitively this would make sense, as emotion regulation and executive functioning are both strongly related to mPFC functionality (Goodell et al 2017). In addition, a decrease in executive functioning has previously been linked to an increase in physical aggression, supporting the notion that mPFC functionality would be involved.…”

“…In a study using optogenetic stimulation, increased stimulation of the mPFC demonstrated a decrease in aggression in mice; optogenetic silencing, on the other hand, showed a marked increase of aggressive behaviors (Takahashi et al 2014). Demonstrating increases of FOS (a family of genes responsible for regulating cell proliferation, transformation, and differentiation) in the prelimbic area (PL), results from Goodell et al (2017) support previous findings that socially dominant mice expressed higher levels of the c-FOS gene in the PL subregion of the mPFC (Wang et al 2011). Their results indicate an elevation in social rank when rodents interact with other nonaggressive rats, revealing mPFC functional sensitivity to the behavioral characteristics of stimulus rats.…”

Social Isolation Rearing Induces Neuropsychiatric Diseases: Updated Overview

“…Affected are NMDA receptors in mice after 3 months of social isolation [41], interneurons in mice [42], and central cannabinoid, serotonergic, and cholinergic systems in rats [43]. Aggressive behavior is influenced by social isolation rearing through prefrontal cortex activation [44]. The hippocampus is another brain region that is influenced by social isolation rearing.…”