Rapid Effects of Corticosterone in the Mouse Dentate Gyrus Via a Nongenomic Pathway

Abstract

Corticosterone activates two types of intracellular receptors in the rodent brain: the high affinity mineralocorticoid receptor (MR) and lower affinity glucocorticoid receptor (GR). These receptors act as transcriptional regulators and mediate slow changes in neuronal activity in a region-dependent manner. For example, in CA1 pyramidal cells, corticosterone slowly changes Ca(2+) currents and glutamate transmission but dentate granule cells appear to be resistant. Recent studies have shown that corticosteroids also exert rapid MR-dependent, nongenomic effects on hippocampal CA1 cells [e.g. increasing the frequency of miniature excitatory postsynaptic currents (mEPSCs)]. In the present study, we investigated whether dentate granule cells are also resistant to the rapid effects of corticosterone. We found that, comparable to the CA1 area, corticosterone quickly and reversibly increases mEPSC frequency but not amplitude of dentate cells. This effect did not require protein synthesis and displayed the pharmacological profile of an MR- rather than GR-dependent event. These data support the hypothesis that, unlike the slow gene-mediated effects of corticosterone, rapid hormonal actions are quite similar for CA1 and dentate cells.

Rapid non-genomic effects of corticosteroids and their role in the central stress response

“…3B). This effect was recently reproduced by other investigators (Qiu et al 2010) and granule neurons in the dentate gyrus respond similarly to corticosterone as CA1 neurons (Pasricha et al 2011). Similar to the corticosteroid effect in the hypothalamus, the rapid effect in the hippocampus does not depend on gene transcription and involves a membrane-located receptor (Karst et al 2005).…”

Unraveling the Time Domains of Corticosteroid Hormone Influences on Brain Activity: Rapid, Slow, and Chronic Modes

“…The MR-dependent increase in mEPSC frequency requires expression of limbic system-associated membrane protein, Lsamp (Qiu et al, 2010). A highly similar MR-dependent raise in mEPSC frequency was observed in granule cells of the dentate gyrus (Pasricha et al, 2011).…”

“…The enhanced mEPSC frequency reported for rapid corticosteroid actions clearly requires MRs (Karst et al, , 2010Olijslagers et al, 2008;Qiu et al, 2010;Pasricha et al, 2011). The suppression of mEPSC or enhancement of sIPSC frequency, via NO or endocannabinoid, seems to involve GRs (Di et al, , 2005Hu et al, 2010;Karst et al, 2010), although mifepristone was usually ineffective, and solid proof for a role of the GR gene was provided only in one study (Karst et al, 2010).…”

Nongenomic glucocorticoid receptor action regulates gap junction intercellular communication and neural progenitor cell proliferation

“…The principal effects of GCs are mediated by transcriptional responses (i.e., activation or repression) that follow either direct binding of a GR-ligand complex to glucocorticoid response elements contained within target genes, or the indirect association of the receptor with other DNA elements or DNA-bound transcription factors (1). However, the GR may also act via nongenomic mechanisms to mediate rapid cellular responses to GCs in the absence of measurable alterations in gene expression (1)(2)(3).…”