Rapid changes in hippocampal CA1 pyramidal cell function via pre- as well as postsynaptic membrane mineralocorticoid receptors

Eur J Neurosci. 2008 May;27(10):2542-50. doi: 10.1111/j.1460-9568.2008.06220.x.


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 microm) and PD098059 (40 microm) and occluded in H-Ras(G12V)-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 I(A) currents. This effect takes place via postsynaptic membrane MRs coupled to a G protein-mediated pathway, as the effect of corticosterone on I(A) was effectively blocked by 0.5 mm GDP-beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / metabolism*
  • Animals
  • Enzyme Inhibitors / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Guanosine Diphosphate / analogs & derivatives
  • Guanosine Diphosphate / pharmacology
  • Hippocampus / metabolism*
  • Hippocampus / ultrastructure
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinase 3 / drug effects
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism*
  • Pyramidal Cells / ultrastructure
  • Receptors, G-Protein-Coupled / drug effects
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Mineralocorticoid / drug effects
  • Receptors, Mineralocorticoid / metabolism*
  • Stress, Physiological / metabolism
  • Stress, Physiological / physiopathology
  • Synaptic Membranes / drug effects
  • Synaptic Membranes / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Thionucleotides / pharmacology


  • Adrenal Cortex Hormones
  • Enzyme Inhibitors
  • Receptors, G-Protein-Coupled
  • Receptors, Mineralocorticoid
  • Thionucleotides
  • Guanosine Diphosphate
  • guanosine 5'-O-(2-thiodiphosphate)
  • Mitogen-Activated Protein Kinase 3