258 history of early stress—were found to have a reduced hippocampal volume (Vythilingam et al. 2002). Also, it should be noted that depressed patients were often exposed to a combination of stress during early life and adulthood; the latter one was not the case in our animal model. The DG is a filter for incoming information into the hippocampus and is thought to separate (spatial) informa- tion input that is highly similar in content, which, in rodents, contributes to (among others) spatial navigation (Scharfman 2007). Changes in DG structure and function may therefore affect downstream processing by the hippo- campus; in accordance, alterations in structural plasticity, e.g. adult neurogenesis, have been shown to affect hippocampus-dependent learning and memory also in relation to its functional role as pattern separator (Clelland et al. 2009; Creer et al. 2010). Despite these findings, the structural changes in adult female rats with a history of MD as seen in this study seem to have no major consequences for DG synaptic plasticity or for hippocampus-dependent learning and memory processes, at least not in the presently used tasks. Whether additional challenges at an adult age would induce such deficits awaits future research. Rather, concurrent with the structural changes in the hippocampus, amygdala function may be altered in these females as a consequence of MD. Excessive amygdala activation to fearful situations is a consistent finding in depressed individuals (Abercrombie et al. 1998; Drevets et al. 1992; Leppanen 2006). We therefore speculate that a change in HPA levels due to early life stress may contribute to structural changes in limbic areas. This could eventually cause behavioural dysfunction, particularly the processing of emotional (rather than neutral) events. Acknowledgements PJL was supported by the Hersenstichting Nederland, the EU (NEURAD consortium), ISAO and the Volkswa- gen Stiftung Germany; the authors declare that they have no conflict of interest. We would like to thank Els Velzing (Swammerdam Institute for Life Sciences, University of Amsterdam, The Nether- lands) for technical assistance, Joop van Heerikhuize (Netherlands Institute for Neuroscience, Amsterdam, The Netherlands) for assis- tance with the Neurodraw software and Maaike van der Mark (Leiden/ Amsterdam Center for Drug Research, Leiden University, The Netherlands) for the analysis of plasma corticosterone levels. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which per- mits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. 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