Psychopharmacology (2011) 214:249–260 studies have reported effects of the early life environment on dendritic complexity in various hippocampal sub-fields, but this was mainly done in males and compared either natural levels of maternal care (Bagot et al. 2009; Champagne et al. 2008) or studied low maternal care induced after chronic stress (Brunson et al. 2005). In these studies, a reduction in dendritic mass, dendritic complexity and spine density was found. The results from the present study do not reveal an overall dendritic atrophy or loss of complexity but rather a higher number of primary dendrites, which is usually a sign of more mature neurons (Claiborne et al. 1990). Our results therefore suggest that a surge in postnatal corticosteroid levels due to MD—even though basal hormone levels are lower in adult females—yields fewer granular cells in female offspring. Yet, these cells do have a more mature phenotype. Functional consequences of maternal deprivation Chronic early life stress and low levels of maternal care are known to impair LTP in area CA3 (Brunson et al. 2005), CA1 (Champagne et al. 2008) and in the DG (Bagot et al. 2009). MD also impairs stress-induced late-phase LTP reinforcement in the DG (Gruss et al. 2008). However, all these studies were performed in males. In the present study, no effects of MD were found on LTP in the DG of female rats, nor did corticosterone application affect LTP in control or MD animals. This indicates that a reduced GCL number and density and an altered dendritic complexity do not necessarily influence the ability to elicit synaptic plasticity. In this study, we stimulated the medial perforant path and recorded the fEPSP from the molecular layer. A possible explanation for the lack of MD-induced effects on LTP could be that putative effects on synaptic transmission are only expressed at other (presently not investigated) synaptic inputs to the DG. An alternative explanation could be that the changes in DG cell number are compensated for by the changes in dendritic morphology. In the present study, females exposed to 24 h MD on PND 3 were not altered in their performance in the water maze, a spatial learning task dependent on an intact hippocampus (Schenk and Morris 1985). Other studies have shown an impairment of water maze acquisition after MD, but these were mostly carried out in males (Aisa et al. 2007; Choy et al. 2008; Garner et al. 2007; Mello et al. 2009; Oitzl et al. 2000; Uysal et al. 2005). One study regarding the effects of MD on spatial learning in females found an enhanced acquisition (Pryce and Feldon 2003), as opposed to an impairment in males. In our model, we also found such a differential, sex-dependent effect of MD on spatial acquisition since water maze learning was impaired in male offspring after MD (Oomen et al. 2010), but not in females as shown in the current study. 257 In addition to the water maze data, we found that the memory of a fearful context was unchanged after MD. Our combined electrophysiological and behavioural data therefore suggest that, in female rodents, 24 h MD at PND 3 does not profoundly alter hippocampal function later in life despite the changes in total cell number and primary dendrites per cell in the DG. MD females did show an enhanced freezing response to the tone when tested for retention in a cued fear conditioning paradigm. Remarkably, freezing behaviour was already elevated before the tone. This indicates that, after MD, females show overall higher anxiety levels, but this was not confirmed by data on the training phase of fear conditioning, contextual fear conditioning nor by their behaviour in the elevated plus maze. The differences in cue fear conditioning may therefore reflect a specific increase in the memory of emotional events. Fear condi- tioning can be modulated (to some extent) by changes in the corticosteroid level (Cordero et al. 1998; Pugh et al. 1997), and for this reason, we measured corticosterone levels after exposure to an adverse novel environment in experiment I. Yet, it seems unlikely—although it cannot be ruled out completely—that the effects of MD on cued fear conditioning are mediated by MD-dependent differences in circulating levels of corticosterone at the time of training or retention since we did not observe significant effects of MD on stress-induced corticosterone levels. Instead, we observed decreased basal levels of corticosterone after MD, both at PND 21 and in 2- to 3-month-old female rats. An alternative explanation is that MD may have altered dendritic complexity of principal neurons in the basolateral amygdala, which is believed to be critical for cued memory (LeDoux et al. 1988; Rodrigues et al. 2009). We here showed that a severe model of early life stress reduces GCL number and density and induces an altered neuronal morphology in the DG of female offspring. This indicates that, although the prominent changes in neurogenesis at 3 weeks after MD (Oomen et al. 2009) normalise, it may eventually have long-lasting consequences for total neuron numbers. Whether similar changes occur with respect to hippocampal volume reduction in depressive patients remains to be shown (Czeh and Lucassen 2007). Analysis of postmortem hippocampus tissue of depressed patients has revealed minor structural alterations at the level of astrocyte (Muller et al. 2001), cytogenesis (Boldrini et al. 2009; Lucassen et al. 2010b) and neuron (Stockmeier et al. 2004) density, but possible changes in total neuron numbers have not been addressed. Such studies are required to reveal a relationship between our observation that early stress in rodents is able to produce irreversible changes in cell numbers of the hippocampus in female offspring and the notion that depressed women—in particular those with a