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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.

Abstract: As the key neuron-to-neuron interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. However, the signal transduction mechanisms by which stress mediates its lasting effects on synapse transmission and on memory are not fully understood. A key component of the stress response is the increased secretion of adrenal steroids. Adrenal steroids (e.g., cortisol) bind to genomic mineralocorticoid and glucocorticoid receptors (gMRs and gGRs) in the cytosol. In addition, they may act through membrane receptors (mMRs and mGRs), and signal transduction through these receptors may allow for rapid modulation of synaptic transmission as well as modulation of membrane ion currents. mMRs increase synaptic and neuronal excitability; mechanisms include the facilitation of glutamate release through extracellular signal–regulated kinase signal transduction. In contrast, mGRs decrease synaptic and neuronal excitability by reducing calcium currents through N-methyl-D-aspartate receptors and voltage-gated calcium channels by way of protein kinase A– and G protein–dependent mechanisms. This body of functional data complements anatomical evidence localizing GRs to the postsynaptic membrane. Finally, accumulating data also suggest the possibility that mMRs and mGRs may show an inverted U–shaped dose response, whereby glutamatergic synaptic transmission is increased by low doses of corticosterone acting at mMRs and decreased by higher doses acting at mGRs. Thus, synaptic transmission is regulated by mMRs and mGRs, and part of the stress signaling response is a direct and bidirectional modulation of the synapse itself by adrenal steroids.

* 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).

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