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

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   Figure 1

   The limbic system is implicated in adaptation, learning and memory processes, mood and control of the HPA-axis. The hormones of the HPA-axis coordinate information processing and promote connectivity between amygdala, prefrontal cortex and hippocampus to facilitate behavioural adaptation. Projections from the limbic structures innervate the PVN network and regulate trans-synaptically the activity of the HPA-axis.
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   Figure 2

   Model of the present knowledge regarding the synaptic pathways of corticosterone-induced rapid effects on glutamatergic transmission. (A) Inhibition of glutamatergic transmission is initiated by postsynaptically located receptors; this can be either G-protein-coupled receptors (hypothalamus) or membrane-localized GRs (amygdala). Activation of these receptors by corticosterone induces activation of G-proteins and the cAMP-protein kinase A (PKA) pathway, which eventually induces synthesis of the retrograde messengers anandamide (AEA) and 2-arachidonoylglycerol (2-AG). In a retrograde mode of action 2-AG and AEA activate the cannabinoid receptor type 1 (CB1) at the presynaptic terminal, which in turn inhibits the release probability of glutamatergic vesicles. (B) Facilitation of glutamatergic transmission is initiated by both pre- and post-synaptically located membrane-MRs. Presynaptically, activation of the MR by corticosterone activates an extracellular signal-regulated kinase (ERK) pathway, resulting in stimulation of the release probability of glutamate vesicles. At the same time, postsynaptic activation of a membrane-associated MR inhibits potassium I_A-currents, and stimulates membrane diffusion of AMPA receptors. All three effects together result in a facilitation of glutamatergic transmission.
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   Figure 3

   Effect of two pulses of corticosterone on mEPSC frequency in the CA1 region and the basolateral amygdala (BLA). (A) Typical traces of mEPSC pulses recorded from BLA neurons before and after treatment with 100 nM corticosterone. (B) In hippocampal CA1 neurons, exposed to two consecutive pulses of 100 nM corticosterone (1 h apart), both pulses induce a reversible increase in mEPSC frequency. (C) In amygdalar BLA neurons, the first pulse of corticosterone induces an increase in mEPSC frequency, which is not reversible. For the second pulse of corticosterone, the basal mEPSC frequency is already elevated and the second pulse induces an irreversible decrease instead. mEPSC, miniature excitatory postsynaptic current. *P<0.05 compared with baseline (paired t-test). Figure reprinted with permission from Karst et al. (2010).
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   Figure 4

   A putative model of the temporal dynamics of excitability in the hippocampus, amygdala and hypothalamus. A stressor or corticosterone injection induces a temporal diverse set of responses in the three different brain areas. Denoted are the receptors that are (mainly) responsible for the effects in the different areas. Importantly, the temporal pattern of excitability in hippocampus, amygdala and hypothalamus determines the actions of stress and corticosterone on neuroendocrine regulation, behaviour and cognition. mMR/mGR, membrane-associated MR/GR; gGR, genomic GR; GPCR, G-protein coupled receptor.

• © 2011 Society for Endocrinology