Early maternal deprivation affects dentate gyrus structure and emotional learning in adult female rats

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 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.

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.

Fig. 1

Effects of MD on the granule cell layer of the hippocampal dentate gyrus. a MD treatment caused a significant reduction in absolute granule cell numbers (p = 0.04) as well as b cell density (p = 0.03; both groups n = 8)

Fig. 2

Effects of MD on synaptic plasticity. a LTP measured under vehicle conditions (CON n = 7, MD n = 7). There was no effect of maternal deprivation on the degree of LTP in the dentate gyrus after theta burst stimulation (CON vs. MD; F _1,28 = 0.03; p = 0.86) when comparing the second half of baseline recordings (t = −10 to 0 min) with post-TBS recordings. b Long-term potentiation after acute corticosterone application. The degree of LTP was not affected by corticosterone application, and there was no difference between CON (n = 7) and MD (n = 7) animals (F _1,28 = 0.04; p = 0.84), interaction group × treatment (F _1,28 = 0.002; p = 0.96)

Fig. 3

Effects of MD on water maze acquisition. Travel distance to the hidden platform was similar in both CON and MD animals (both groups n = 10; p = 0.16)

Fig. 4

Effects of MD on fear conditioning. a MD does not affect the amount of freezing behaviour in response to the context (p = 0.35). b During cued fear conditioning, MD animals (n = 10) show increased freezing in response to the novel environment (p = 0.002) and an increased freezing behaviour in response to the tone when compared to controls (both groups, n = 10, p < 0.05)