MR mediated effects in the brain
The MR became a central focus as a moderator of early stress responses since the receptor was found to mediate non-genomic rapid and transient effects of corticosteroids on neurotransmission and synaptic plasticity in the hippocampus and amygdala after stress (Karst and Joëls, 2005; Karst et al. , 2010; Nahar et al. , 2015; Treviño and Gorelick, 2021). This was specifically shown with the rapid and transient increase of miniature excitatory postsynaptic currents (mEPSC) following treatment with corticosterone, whereby signaling was transduced by MRs located pre-synaptically at the plasma membrane regulating the eventual release of glutamate, in contrast to genomic receptors (Karst et al. , 2010; Groeneweg et al. , 2012). A distinct mechanism of non-genomic MR signaling could involve receptor dissociation from chaperone complexes within the cytoplasm (Gutierrez-Mecinas et al. , 2011) in concert with mediators like noradrenalin and CRH. Of note, non-genomic MR effects can determine subsequent genomic mechanisms, which has been termed metaplasticity (Karst et al. , 2010; Chatterjee and Sikdar, 2014; Sarabdjitsinghet al. , 2014).