Membrane associated synaptic mineralocorticoid and glucocorticoid receptors are rapid regulators of dendritic spines

Unemployment is never a good situation to be in. For ~25 years the direct membrane acting, non-genomic, variety of the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) have been in want of a credible function. Even the existence of a membrane MR (mMR) and membrane GR (mGR) was questioned. Recent data suggest this is changing; mMR and mGR are located in synapses and surrounding space of rapidly plastic dendritic spines (Prager et al., 2010; Komatsuzaki et al., 2012; Yoshiya et al., 2013). Emerging evidence, reviewed below, links mGR activation to rapid changes in dendritic spine size and number. These structural changes can be both experimentally induced and are also naturally induced during circadian fluctuations in corticosterone levels, and are rapidly mediated by kinase signaling. Moreover, mMR activation may reverse these changes. Previous data also links the mMR to receptor trafficking and regulation of synaptic transmission. Collectively mMR and mGR mediated rapid regulation of synaptic structure and function is central for learning and memory. In this paper we briefly summarize the history of the mMR and mGR and then update on the emerging evidence of their reported functions. Here we argue that there is enough evidence to consider these rapidly acting non-genomic membrane receptors as members of the community of fully employed receptors.