Karst H, Berger S, Turiault M, Tronche F, Scutz G, Joels M. Mineralocorticoid receptors are indispensable for nongenomlc modulation of hippocampal glutamate transmission by corticosterone. Proc Natl Acad Sci USA 102: 19204-19207

Swammerdam Institute for Life Sciences, Center for Neurosciences (SILS-CNS), University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 01/2006; 102(52):19204-7. DOI: 10.1073/pnas.0507572102
Source: PubMed


The adrenal hormone corticosterone transcriptionally regulates responsive genes in the rodent hippocampus through nuclear mineralocorticoid and glucocorticoid receptors. Via this genomic pathway the hormone alters properties of hippocampal cells slowly and for a prolonged period. Here we report that corticosterone also rapidly and reversibly changes hippocampal signaling. Stress levels of the hormone enhance the frequency of miniature excitatory postsynaptic potentials in CA1 pyramidal neurons and reduce paired-pulse facilitation, pointing to a hormone-dependent enhancement of glutamate-release probability. The rapid effect by corticosterone is accomplished through a nongenomic pathway involving membrane-located receptors. Unexpectedly, the rapid effect critically depends on the classical mineralocorticoid receptor, as evidenced by the effectiveness of agonists, antagonists, and brain-specific inactivation of the mineralocorticoid but not the glucocorticoid receptor gene. Rapid actions by corticosterone would allow the brain to change its function within minutes after stress-induced elevations of corticosteroid levels, in addition to responding later through gene-mediated signaling pathways.

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Available from: François Tronche
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    • "For example, a single dose of glucocorticoids administered in rodents led to prolonged expansion of basolateral amygdala neurons that correlated with increased anxiety-like behavior (Mitra and Sapolsky, 2008), suggesting it might also impair or slow extinction learning. Research in rodents has shown that in the amygdala elevated levels of circulating cortisol can bind to GRs within the CE leading to increased excitability (Karst et al., 2005) and dendritic hypertrophy (Mitra and Sapolsky, 2008). In the presence of an extinguished CS, these changes could potentially enhance fear expression by disrupting inhibitory circuits locally within the amygdala. "
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    • "CORT can directly alter neurotransmission by acting on glucocorticoid and mineralocorticoid receptors (GR/MR) and also indirectly by increasing endocannabinoid production [Popoli et al., 2012]. Fast effects of CORT on the hippocampus and amygdala are established by rapid release of glutamate, and most likely involve nongenomic MR function [Groeneweg et al., 2011; Karst et al., 2005; Popoli et al., 2012]. Slower effects of CORT can be directly induced by genomic effects on nuclear GRs [Oitzl et al., 2010] and also indirectly by upregulation of endocannabinoids , resulting in inhibition of the release of glutamate and GABA [Popoli et al., 2012]. "
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    • "Traditionally, animal research has focused on the effects of corticosteroids on HC, where corticosteroids' genomic effects have been known for decades to suppress neuronal excitability (Joëls and de Kloet, 1989; Kerr et al., 1989) and long-term potentiation (LTP) (Pavlides et al., 1995; Wiegert et al., 2005), the alleged neurobiological substrate of memory formation (Martin and Morris, 2002). However, recent findings indicated that corticosteroids increase hippocampal neuronal excitability (Karst et al., 2005) and LTP (Korz and Frey, 2003; Wiegert et al., 2006) in a rapid, non-genomic fashion, but only when present around the time when LTP is induced. Similar excitatory rapid effects have been also observed in AMY (Karst et al., 2010). "
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