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.

RationaleStress 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.ObjectiveWe examined the effects of maternal absence on structure and function of the hippocampus in female offspring.MethodsWe 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.ResultsAdult females that were subjected to MD revealed significant reductions in DG granule cell number and density. In addition, DG neurons were altered in their 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 contextual fear conditioning were comparable between control and MD animals. However, MD animals showed an improved amygdala-dependent fear memory.ConclusionAlthough 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.