Mineralocorticoid Receptors Guide Spatial and Stimulus-Response Learning in Mice

Abstract

Adrenal corticosteroid hormones act via mineralocorticoid (MR) and glucocorticoid receptors (GR) in the brain, influencing learning and memory. MRs have been implicated in the initial behavioral response in novel situations, which includes behavioral strategies in learning tasks. Different strategies can be used to solve navigational tasks, for example hippocampus-dependent spatial or striatum-dependent stimulus-response strategies. Previous studies suggested that MRs are involved in spatial learning and induce a shift between learning strategies when animals are allowed a choice between both strategies. In the present study, we further explored the role of MRs in spatial and stimulus-response learning in two separate circular holeboard tasks using female mice with forebrain-specific MR deficiency and MR overexpression and their wildtype control littermates. In addition, we studied sex-specific effects using male and female MR-deficient mice. First, we found that MR-deficient compared to control littermates and MR-overexpressing mice display altered exploratory and searching behavior indicative of impaired acquisition of novel information. Second, female (but not male) MR-deficient mice were impaired in the spatial task, while MR-overexpressing female mice showed improved performance in the spatial task. Third, MR-deficient mice were also impaired in the stimulus-response task compared to controls and (in the case of females) MR-overexpressing mice. We conclude that MRs are important for coordinating the processing of information relevant for spatial as well as stimulus-response learning.

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: The brain mineralocorticoid receptor: a saga in three episodes

“…application of the MR antagonist spironolactone. If the MR is blocked, the animals maintain the original spatial strategy (Schwabe et al 2010, Arp et al 2014. Similar behavioural observations were made in humans, in various tasks.…”

Stress and Depression: a Crucial Role of the Mineralocorticoid Receptor

“…By inference, MRs are therefore also important for encoding and memory of the situation for future use. This has been demonstrated in both humans and rodents, as well as across many different cognitive domains, including emotional and spatial memory formation and instrumental learning . As such, this role is complemented by that of GR engaged in the consolidation of memory and behavioural adaptation .…”

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).…”