Early life stress determines the effects of glucocorticoids and stress on hippocampal function: Electrophysiological and behavioral evidence respectively

Anup G. Pillai, Marit Arp, Els Velzing, Sylvie L. Lesuis, Mathias V. Schmidt, Florian Holsboer, Marian Joels, Harm J. Krugers*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    14 Citations (Scopus)
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    Abstract

    Exposure to early-life adversity may program brain function to prepare individuals for adaptation to matching environmental contexts. In this study we tested this hypothesis in more detail by examining the effects of early-life stress - induced by raising offspring with limited nesting and bedding material from postnatal days 2-9 - in various behavioral tasks and on synaptic function in adult mice. Early-life stress impaired adult performance in the hippocampal dependent low-arousing object-in-context recognition memory task. This effect was absent when animals were exposed to a single stressor before training. Early-life stress did not alter high-arousing context and auditory fear conditioning. Early-life stress-induced behavioral modifications were not associated with alterations in the dendritic architecture of hippocampal CA1 pyramidal neurons or principal neurons of the basolateral amygdala. However, early-life stress reduced the ratio of NMDA to AMPA receptor-mediated excitatory postsynaptic currents and glutamate release probability specifically in hippocampal CA1 neurons, but not in the basolateral amygdala. These ex vivo effects in the hippocampus were abolished by acute glucocorticoid treatment. Our findings support that early-life stress can hamper object-in-context learning via pre- and post synaptic mechanisms that affect hippocampal function but these effects are counteracted by acute stress or elevated glucocorticoid levels. (C) 2018 Published by Elsevier Ltd.

    Original languageEnglish
    Pages (from-to)307-318
    Number of pages12
    JournalNeuropharmacology
    Volume133
    DOIs
    Publication statusPublished - 1-May-2018

    Keywords

    • Early life adversity
    • Synapses
    • Stress
    • AMPA
    • NMDA
    • Memory
    • SYNAPTIC PLASTICITY
    • MATERNAL-CARE
    • BASOLATERAL AMYGDALA
    • STRUCTURAL PLASTICITY
    • CONTEXT RECOGNITION
    • PYRAMIDAL NEURONS
    • MALE RATS
    • MEMORY
    • MICE
    • CA1

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