title: Hippocampal Fast Glutamatergic Transmission Is Transiently Regulated by Corticosterone Pulsatility.
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.
authors.affiliation: Dept. Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: R Angela
authors.initials: RA
authors.lastname: Sarabdjitsingh
authors.affiliation: Dept. Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.|Universite de Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.|CNRS, IINS UMR 5297, Bordeaux, France.
authors.forename: Natasha
authors.initials: N
authors.lastname: Pasricha
authors.affiliation: Dept. Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Johanna A S
authors.initials: JA
authors.lastname: Smeets
authors.affiliation: Dept. Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.|Universite de Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.|CNRS, IINS UMR 5297, Bordeaux, France.
authors.forename: Amber
authors.initials: A
authors.lastname: Kerkhofs
authors.affiliation: Universite de Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.|CNRS, IINS UMR 5297, Bordeaux, France.
authors.forename: Lenka
authors.initials: L
authors.lastname: Mikasova
authors.affiliation: Dept. Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: Karst
authors.affiliation: Universite de Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.|CNRS, IINS UMR 5297, Bordeaux, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Groc
authors.affiliation: Dept. Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marian
authors.initials: M
authors.lastname: Joëls
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D003345:Corticosterone / Q000378:metabolism / Q000494:pharmacology*; D004622:Embryo, Mammalian; D005071:Evoked Potentials / Q000187:drug effects* / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008867:Microtomy; D057054:Molecular Imaging; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D061251:Primary Cell Culture; D021381:Protein Transport; D045663:Quantum Dots; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2; D003345:Corticosterone