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Sci. Signal., 1 September 2009
Vol. 2, Issue 86, p. re5
[DOI: 10.1126/scisignal.286re5]


Stress at the Synapse: Signal Transduction Mechanisms of Adrenal Steroids at Neuronal Membranes

Eric M. Prager and Luke R. Johnson*

Center for the Study of Traumatic Stress, Department of Psychiatry and Program in Neuroscience, Uniformed Services University, Bethesda, MD 20814, USA.

Gloss: All of us have vivid memories of past stressful events. Although decades of research have identified some of the behavioral principles of the effects of stress on memory, our understanding of the underlying neurobiology is incomplete. Stress itself is a complex phenomenon that can be described on multiple levels, one of which is the activation of the hypothalamic-pituitary-adrenal axis and cortisol release into the blood. The timing of stress on memory formation and memory recall are important, and the effects of cortisol on memory can be rapid, occurring within minutes. Increased cortisol just before and during memory formation enhances memory of the event. In contrast, cortisol elevation during memory recall reduces memory. Cortisol acts on glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs), which have long been known to function as transcription factors. A growing body of subcellular and electrophysiological evidence indicates that cortisol may also promote rapid effects on neuron-to-neuron communication through membrane-located MRs and GRs. The site of neuron-to-neuron communication is the synapse; thus, stress may directly and rapidly regulate the synapse itself. Low concentrations of cortisol at the synapse can increase neurotransmitter release, whereas higher concentrations may dampen excitability by reducing current flow through ion channels. These data may help to explain how stress can be so influential on memory and cognitive performance. This Review, with three figures and 111 citations, highlights the signaling processes by which cortisol may influence neuronal excitability and thereby memory and cognitive performance.

* Corresponding author. E-mail, luke.johnson{at}

Citation: E. M. Prager, L. R. Johnson, Stress at the Synapse: Signal Transduction Mechanisms of Adrenal Steroids at Neuronal Membranes. Sci. Signal. 2, re5 (2009).

Hormones and the Social Brain.
B. S. McEwen (2013)
Science 339, 279-280
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Rapid non-genomic effects of corticosteroids and their role in the central stress response.
F. L. Groeneweg, H. Karst, E. R. de Kloet, and M. Joels (2011)
J. Endocrinol. 209, 153-167
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Pregnenolone Sulfate and Cortisol Induce Secretion of Acyl-CoA-binding Protein and Its Conversion into Endozepines from Astrocytes.
W. F. Loomis, M. M. Behrens, M. E. Williams, and C. Anjard (2010)
J. Biol. Chem. 285, 21359-21365
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