Severe early life stress hampers spatial learning and neurogenesis, but improves hippocampal synaptic plasticity and emotional learning under high-stress conditions in adulthood

Charlotte A. Oomen, Heleen Soeters, Nathalie Audureau, Lisa Vermunt, Felisa N. Van Hasselt, Erik M.M. Manders, Marian Joëls, Paul J. Lucassen, Harm Krugers

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Early life stress increases the risk for developing stress-related pathologies later in life. Recent studies in rats suggest that mild early life stress, rather than being overall unfavorable, may program the hippocampus such that it is optimally adapted to a stressful context later in life. Here, we tested whether this principle of "adaptive programming" also holds under severely adverse early life conditions, i.e., 24 h of maternal deprivation (MD), a model for maternal neglect. In young adult male rats subjected to MD on postnatal day 3, we observed reduced levels of adult hippocampal neurogenesis as measured by cell proliferation, cell survival, and neuronal differentiation. Also, mature dentate granule cells showed a change in their dendritic morphology that was most noticeable in the proximal part of the dendritic tree. Lasting structural changes due to MD were paralleled by impaired water maze acquisition but did not affect long-term potentiation in the dentate gyrus. Importantly, in the presence of high levels of the stress hormone corticosterone, even long-term potentiation in the dentate gyrus of MD animals was facilitated. In addition to this, contextual learning in a high-stress environment was enhanced in MD rats. These morphological, electrophysiological, and behavioral observations show that even a severely adverse early life environment does not evolve into overall impaired hippocampal functionality later in life. Rather, adversity early in life can prepare the organism to perform optimally under conditions associated with high corticosteroid levels in adulthood.

Original languageEnglish
Pages (from-to)6635-6645
Number of pages11
JournalJournal of Neuroscience
Issue number19
Publication statusPublished - 12 May 2010

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