Psychopharmacology (2011) 214:249–260 DOI 10.1007/s00213-010-1922-8 ORIGINAL INVESTIGATION Early maternal deprivation affects dentate gyrus structure and emotional learning in adult female rats Charlotte A. Oomen & Heleen Soeters & Nathalie Audureau & Lisa Vermunt & Felisa N. van Hasselt & Erik M. M. Manders & Marian Joëls & Harm Krugers & Paul J. Lucassen Received: 30 March 2010 / Accepted: 9 June 2010 / Published online: 30 June 2010 # The Author(s) 2010. This article is published with open access at Springerlink.com Abstract Rationale Stress elicits functional and structural changes in the hippocampus. Early life stress is one of the major risk factors for stress-related pathologies like depression. Patients suffering from depression show a reduced hippocampal volume, and in women, this occurs more often when depression is preceded by childhood trauma. However, the underlying mechanisms that account for a reduced hippocampal volume are unknown. Objective We examined the effects of maternal absence on structure and function of the hippocampus in female offspring. Methods We studied whether 24 h of maternal deprivation (MD) on postnatal day 3 altered adult neurogenesis, individual neuronal morphology and dentate gyrus (DG) structure in young adult female rats. In addition, functional alterations were addressed by studying synaptic plasticity in vitro, and spatial as well as emotional learning was tested. Results Adult females that were subjected to MD revealed significant reductions in DG granule cell number and density. In addition, DG neurons were altered in their C. A. Oomen (*) : H. Soeters : N. Audureau : L. Vermunt : F. N. van Hasselt : M. Joëls : H. Krugers : P. J. Lucassen Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands e-mail: c.a.oomen@uva.nl P. J. Lucassen e-mail: P.J.Lucassen@uva.nl E. M. M. Manders Center for Advanced Microscopy, University of Amsterdam, Amsterdam, The Netherlands M. Joëls Rudolf Magnus Institute for Neurosciences, UMC Utrecht, Utrecht, The Netherlands dendritic arrangement. No effects on the rate of adult neurogenesis were found. Furthermore, MD did not alter synaptic plasticity in vitro, neither under normal nor high- stress conditions. In addition, spatial learning and contex- tual fear conditioning were comparable between control and MD animals. However, MD animals showed an improved amygdala-dependent fear memory. Conclusion Although early life stress exposure did not impair hippocampus-dependent functioning in female offspring, it irreversibly affected DG structure by reducing cell numbers. This may be relevant for the reduced hippocampal volume observed in depression and the increased vulnerability of women to develop depression. Keywords Rats . Females . Maternal deprivation . Stress . Dentate gyrus . Hippocampus . Adult neurogenesis . Long-term potentiation . Learning and memory Introduction Epidemiological studies suggest that major depression is more prevalent in women than in men (Bland 1997; Kessler et al. 1993; Ustun 2000). However, the exact neurobiological mechanisms that may account for this selective vulnerability remain unknown. The hippocampus, a brain region involved in learning and memory, is susceptible to the effects of stress and shows a reduced volume in depressive patients (Axelson et al. 1993; Bremner et al. 2000; Campbell et al. 2004; Janssen et al. 2004; Sheline et al. 1999; Videbech and Ravnkilde 2004). Interestingly, hippocampal volume reduction particularly occurred in women who were exposed to early childhood trauma (Vythilingam et al. 2002). This suggests that early life stress—possibly via changes in hippocampus structure and function—forms a risk factor for the development of