Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone.
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.
Karst
Henk
H
Swammerdam Institute for Life Sciences, Center for Neurosciences (SILS-CNS), University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands. karst@science.uva.nl
Berger
Stefan
S
Turiault
Marc
M
Tronche
Francois
F
Schütz
Günther
G
Joëls
Marian
M
D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003345:Corticosterone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004566:Electrodes; D019706:Excitatory Postsynaptic Potentials; D016678:Genome; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015735:Mifepristone / Q000494:pharmacology; D008901:Mineralocorticoids / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D005971:Glutamates; D008901:Mineralocorticoids; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D015735:Mifepristone; D018698:Glutamic Acid; D003345:Corticosterone