Mineralocorticoid receptor deletion alters spontaneous behavior in an automated home-cage monitoring apparatus

Mineralocorticoid receptors (MRs) are transcription factors expressed throughout the body and brain, with especially high expression in the hippocampal area CA2. MRs are essential for maintaining the physiological stress response and regulating the hypothalamic-pituitary adrenal (HPA) axis. Further, MRs function through the diurnal modulation of corticosterone activity. The aim of the current study was to determine the role MRs play in the modulation of spontaneous behavior throughout the day/night cycle. Three conditional MR knockout mouse lines were utilized: one with broad embryonic neuronal deletion (Nestin-Cre), one with embryonic forebrain deletion (EMX-Cre), and one with postnatal CA2-targeted deletion (Amigo2-Cre). Behavior in these strains was assessed using an automated home cage monitoring system to track spontaneous behavior over a 60-h period. Broad deletion of MRs disrupted behavior in a sex-dependent manner, with alteration in motor activity and shelter behavior at night. Forebrain deletion of MRs produced similar, but less pronounced, differences in motor activity and shelter behavior, while CA2-targeted deletion produced little alteration in behavior either during the day or at night. These findings provide evidence for the essential role of MRs in the regulation of behavior across the day/night cycle and shed a light on the role of MR development and expression on behavior.