Hippocampal Fast Glutamatergic Transmission Is Transiently Regulated by Corticosterone Pulsatility

R. Angela Sarabdjitsingh*, Natasha Pasricha, Johanna A. S. Smeets, Amber Kerkhofs, Lenka Mikasova, Henk Karst, Laurent Groc, Marian Joels

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

20 Citations (Scopus)
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Abstract

In recent years it has become clear that corticosteroid hormones (such as corticosterone) are released in ultradian pulses as a natural consequence of pituitary-adrenal interactions. All organs, including the brain, are thus exposed to pulsatile changes in corticosteroid hormone level, important to ensure full genomic responsiveness to stress-induced surges. However, corticosterone also changes neuronal excitability through rapid non-genomic pathways, particularly in the hippocampus. Potentially, background excitability of hippocampal neurons could thus be changed by pulsatile exposure to corticosteroids. It is currently unknown, though, how neuronal activity alters during a sequence of corticosterone pulses. To test this, hippocampal cells were exposed in vitro to four consecutive corticosterone pulses with a 60 min inter-pulse interval. During the pulses we examined four features of hippocampal signal transfer by the main excitatory transmitter glutamate-i.e., postsynaptic responses to spontaneous release of presynaptic vesicles, postsynaptic GluA2-AMPA receptor dynamics, basal (evoked) field responses, and synaptic plasticity, using a set of high resolution imaging and electrophysiological approaches. We show that the first pulse of corticosterone causes a transient increase in miniature EPSC frequency, AMPA receptor trafficking and synaptic plasticity, while basal evoked field responses are unaffected. This pattern is not maintained during subsequent applications: responses become more variable, attenuate or even reverse over time, albeit with different kinetics for the various experimental endpoints. This may indicate that the beneficial effect of ultradian pulses on transcriptional regulation in the hippocampus is not consistently accompanied by short-term perturbations in background excitability. In general, this could be interpreted as a means to keep hippocampal neurons responsive to incoming signals related to environmental challenges.

Original languageEnglish
Article numbere0145858
Number of pages15
JournalPLoS ONE
Volume11
Issue number1
DOIs
Publication statusPublished - 7-Jan-2016
Externally publishedYes

Keywords

  • STRESS HORMONE CORTICOSTERONE
  • SURFACE TRAFFICKING
  • SYNAPTIC PLASTICITY
  • MINERALOCORTICOID RECEPTORS
  • NEUROTRANSMITTER RECEPTOR
  • GLUCOCORTICOID-RECEPTOR
  • ULTRADIAN RHYTHM
  • HPA AXIS
  • BRAIN
  • RESPONSIVENESS

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