Deletion of the forebrain mineralocorticoid receptor impairs social discrimination and decision-making in male, but not in female mice

Abstract

Social interaction with unknown individuals requires fast processing of information to decide whether it is friend or foe. This process of discrimination and decision-making is stressful and triggers secretion of corticosterone activating mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The MR is involved in appraisal of novel experiences and risk assessment. Recently, we have demonstrated in a dual-solution memory task that MR plays a role in the early stage of information processing and decision-making. Here we examined social approach and social discrimination in male and female mice lacking MR from hippocampal-amygdala-prefrontal circuitry and controls. The social approach task allows the assessment of time spent with an unfamiliar mouse and the ability to discriminate between familiar and unfamiliar conspecifics. The male and female test mice were both more interested in the social than the non-social experience and deletion of their limbic MR increased the time spent with an unfamiliar mouse. Unlike controls, the male MRCaMKCre mice were not able to discriminate between an unfamiliar and the familiar mouse. However, the female MR mutant had retained the discriminative ability between unfamiliar and familiar mice. Administration of the MR antagonist RU28318 to male mice supported the role of the MR in the discrimination between an unfamiliar mouse and a non-social stimulus. No effect was found with a GR antagonist. Our findings suggest that MR is involved in sociability and social discrimination in a sex-specific manner through inhibitory control exerted putatively via limbic-hippocampal efferents. The ability to discriminate between familiar and unfamiliar conspecifics is of uttermost importance for territorial defense and depends on a role of MR in decision-making.

Coping with the Forced Swim Stressor: Towards Understanding an Adaptive Mechanism

“…The studies by Cabib and coworkers, that are summarized in Cabib and Puglisi-Allegra [ 16 ] and Campus et al [ 10 ], point to a genetically determined switch between hippocampus and striatal circuits as a determinant in the choice of behavioural style to cope with the forced swim. Such an MR-induced switch previously was observed in other behavioural paradigms as well [ 82 , 110 , 115 ]. This finding calls for a role of CORT acting via MR during stress, which has been shown crucial for appraisal, immediate coping, response selection, and behavioural flexibility.…”

“…⑤ The information processing during the forced swim is affected by stress history as can be deducted from altered genomic expression in the hippocampus. This hypothesis is based on the following references: [ 14 – 19 , 28 , 30 , 31 , 36 , 50 , 51 , 58 , 64 , 82 , 84 , 94 , 102 , 110 – 114 ]. For more information we refer to the main text of this paper.…”

The effects of different rearing conditions on sexual maturation and maternal care in heterozygous mineralocorticoid receptor knockout mice

“…The less active parenting style and increased fragmentation of maternal behavior in MR +/− F1 dams suggests a broader role of MR in regulating complex patterns of social behavior. Although MR has been studied predominantly in relation to learning and memory (Arp et al, 2014;Berger et al, 2006;Kanatsou et al, 2017), its role in regulating emotion and social behavior is now increasingly supported (Joëls and De Kloet, 2017;Kruk et al, 2013;Ter Horst et al, 2014;Vogel et al, 2016). In humans, an MR SNP in children was found to moderate the effect of sensitive and insensitive parenting on attachment security (Luijk et al, 2011).…”

Novel role for mineralocorticoid receptors in control of a neuronal phenotype

“…CA2 pyramidal cells are further distinguished from neighboring CA1 and CA3 PCs in that they exhibit a unique pattern of gene expression that permits tight regulation of synaptic plasticity at CA3 → CA2 Schaffer collateral synapses [27] and confers sensitivity to the social neuropeptides oxytocin and vasopressin [28,29], which may play a role in social recognition memory and aggression in mice [28][29][30][31][32]. Recent studies have demonstrated that CA2 PCs are important for social memory, aggression, spatial processing, and detection of novelty, behaviors that have also been linked to MRs [28,[32][33][34][35][36]. In this study, we set out to investigate whether deletion of MRs affects CA2 neuron physiology and function.…”