Rapid changes in hippocampal CA1 pyramidal cell function via pre- as well as postsynaptic membrane mineralocorticoid receptors
Corticosterone (100 nm) rapidly increases the frequency of miniature excitatory postsynaptic currents in mouse CA1 pyramidal neurons via membrane‐located mineralocorticoid receptors (MRs). We now show that a presynaptic ERK1/2 signalling pathway mediates the nongenomic effect, as it was blocked by t...
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Published in | The European journal of neuroscience Vol. 27; no. 10; pp. 2542 - 2550 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.05.2008
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Subjects | |
Online Access | Get full text |
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Summary: | Corticosterone (100 nm) rapidly increases the frequency of miniature excitatory postsynaptic currents in mouse CA1 pyramidal neurons via membrane‐located mineralocorticoid receptors (MRs). We now show that a presynaptic ERK1/2 signalling pathway mediates the nongenomic effect, as it was blocked by the MEK inhibitors U0126 (10 µm) and PD098059 (40 µm) and occluded in H‐RasG12V‐mutant mice with constitutive activation of the ERK1/2 presynaptic pathway. Notably, the increase in mEPSC frequency was not mediated by retrograde signalling through endocannabinoids or nitric oxide, supporting presynaptic localization of the signalling pathway. Unexpectedly, corticosterone was also found to have a direct postsynaptic effect, rapidly decreasing the peak amplitude of IA currents. This effect takes place via postsynaptic membrane MRs coupled to a G protein‐mediated pathway, as the effect of corticosterone on IA was effectively blocked by 0.5 mm GDP‐β‐S administered via the recording pipette into the postsynaptic cell. Taken together, these results indicate that membrane MRs mediate rapid, nongenomic effects via pre‐ as well as postsynaptic pathways. Through these dual pathways, high corticosterone concentrations such as occur after stress could contribute to enhanced CA1 pyramidal excitability. |
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Bibliography: | ark:/67375/WNG-J5GQPBML-S istex:50C45E557E06C887E7D2BF20B5D2F190D4EBE9F5 ArticleID:EJN6220 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0953-816X 1460-9568 |
DOI: | 10.1111/j.1460-9568.2008.06220.x |