Karst, H. et al. Mineralocorticoid receptors are indispensable for nongenomic 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

ABSTRACT 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, Sep 26, 2015
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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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    ABSTRACT: Fear learning and regulation is as a prominent model for describing the pathogenesis of anxiety disorders and stress-related psychopathology. Fear expression can be modulated using a number of regulatory strategies, including extinction, cognitive emotion regulation, avoidance strategies and reconsolidation. In this review, we examine research investigating the effects of acute stress and stress hormones on these regulatory techniques. We focus on what is known about the impact of stress on the ability to flexibly regulate fear responses that are acquired through Pavlovian fear conditioning. Our primary aim is to explore the impact of stress on fear regulation in humans. Given this, we focus on techniques where stress has been linked to alterations of fear regulation in humans (extinction and emotion regulation), and briefly discuss other techniques (avoidance and reconsolidation) where the impact of stress or stress hormones have been mainly explored in animal models. These investigations reveal that acute stress may impair the persistent inhibition of fear, presumably by altering prefrontal cortex function. Characterizing the effects of stress on fear regulation is critical for understanding the boundaries within which existing regulation strategies are viable in everyday life and can better inform treatment options for those who suffer from anxiety and stress-related psychopathology.
    01/2015; 1(1):134-146. DOI:10.1016/j.ynstr.2014.11.004
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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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    ABSTRACT: Animal studies show that exposure to parental neglect alters stress regulation and can lead to neural hyposensitivity or hypersensitivity in response to cortisol, most pronounced in the hippocampus. Cortisol, the end product of the hypothalamic-pituitary-adrenal (HPA) axis, has also been related to parenting more directly, for example, in both sexes, cortisol levels increase when listening to infants crying, possibly to activate and facilitate effective care behavior. Severe trauma is known to negatively affect the HPA-axis in humans; however, it is unknown whether normal variation in parental care in the healthy population can alter sensitivity of the hippocampus to cortisol. Here, we investigate whether variation in experienced neglect changes neural sensitivity to cortisol when humans listen to infant crying, which is an unequivocal signal relevant for care behavior. In a placebo-controlled, within-subject neuroimaging study, we administered 40 mg cortisol to 21 healthy young males without children and used a validated task for measuring neural responses to infant crying. The Dutch version of the Childhood Trauma Questionnaire was used to index participants' early exposure to abuse and neglect. The data show that cortisol markedly increased hippocampal activation toward crying infants, and this effect varied significantly with parental neglect, even in our nonclinical subject sample. Without exposure to severe trauma or neglect, reduced self-experienced quality of parental care in the normal range already substantially increased hippocampal responsivity to cortisol. Altered hippocampal sensitivity to cortisol might be a cross-species marker for the risk of developing later life psychopathology. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 10/2014; 35(10). DOI:10.1002/hbm.22537 · 5.97 Impact Factor
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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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    ABSTRACT: A commentary on "Time-dependent effects of cortisol on selective attention and emotional interference: A functional MRI study", by Henckens, M.J.A.G.,van Wingen, G.A., Joëls, M., and Fernández,G.(2012). Front. Integr. Neurosci., 6:66; doi:10.3389/fnint.2012.00066.
    Frontiers in Neuroscience 09/2014; 8(268). DOI:10.3389/fnins.2014.00268 · 3.66 Impact Factor
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