Isolation rearing attenuates social interaction-induced expression of immediate early gene protein products in the medial prefrontal cortex of male and female rats

Abstract

Early life adversity and stress in humans has been related to a number of psychological disorders including anxiety, depression, and addiction. The present study used isolation rearing, a well-characterized animal model of early life adversity, to examine its effects on social behavior and immediate early gene (IEG) expression produced by exposure to a novel social experience. Male and female rats were housed in same-sex groups or in isolation for 4 weeks beginning at weaning and were tested during late adolescence. The protein products of the IEGs c-fos and Arc, as well as the neurotrophic factor BDNF were assessed in medial prefrontal cortex (mPFC) subregions (anterior cingulate, prelimbic and infralimbic) using immunohistochemistry. Aggressive and non-aggressive behaviors during novel social exposure were also assessed. Exposure to a novel conspecific produced increases in Arc and c-fos activation in the mPFC of group reared animals in a sex- and subregion-dependent fashion compared to no social exposure controls, but this increase was blunted or absent in isolated animals. Isolates engaged in more social interactions and more aggressive behavior than group reared rats. Sex differences in some behaviors as well as in Arc and BDNF expression were observed. These results indicate that isolation rearing alters IEG activation in the mPFC produced by exposure to a novel conspecific, in addition to changing social behavior, and that these effects depend in part on sex.

Social Play Behavior in Adolescent Rats is Mediated by Functional Activity in Medial Prefrontal Cortex and Striatum

“…This begs the question of the exact contribution of PrL, IL, and MO/VO in social play behavior, given that their inactivation produces comparable reductions in social play. Interestingly, cellular activation studies have found similar patterns of activity of PrL and IL neurons during social behavior in late adolescent rats (Wall et al, 2012) and during sexual behavior in adult rats (Balfour et al, 2006). Consistent with this, we have recently found comparable increases in c-fos expression in PrL, IL, MO, and VO after social play, although the magnitude of the effect differed somewhat between these regions (Van Kerkhof et al, 2013).…”

Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model

“…Thus, it is possible that loss of M 1 -mediated mLTD at the hippocampo-PFC synapse plays a major role in regulating PFC activation by hippocampal afferents under normal conditions, and that loss of this function contributes to the increased activation of the PFC and resultant behavioral outcomes of dysfunctional recognition memory and social interaction in this rodent model. As normal PFC function is essential for both social interaction (Elliott et al, 2012;Shah and Treit, 2003;Wall et al, 2012) and recognition memory (Bekinschtein and Weisstaub, 2014;Watson et al, 2012) in rodents, this study provides the first direct evidence for a potential role of impaired M 1 -mediated mLTD in PFC as an underlying cause of these behavioral deficits.…”

Social Isolation During Postweaning Development Causes Hypoactivity of Neurons in the Medial Nucleus of the Male Rat Amygdala

“…Rats were used for experiments after 4-5 weeks (P50-60 postadolescents), or at intermediate time points, as described below. Several studies indicate that social behavior in males may be more sensitive to postweaning social isolation (Ferdman et al, 2007;Wall et al, 2012;Ahern et al, 2016). Therefore, males were the focus of the current study.…”