The impact of maternal separation on adult mouse behaviour and on the total neuron number in the mouse hippocampus - PubMed (original) (raw)

The impact of maternal separation on adult mouse behaviour and on the total neuron number in the mouse hippocampus

Katrine Fabricius et al. Brain Struct Funct. 2008 Feb.

Abstract

The maternal separation paradigm has been applied to C57BL/6J mice as an animal developmental model for understanding structural deficits leading to abnormal behaviour. A maternal separation (MS) model was used on postnatal day (PND) 9, where the pups were removed from their mother for 24 h (MS24). When the pups were 10 weeks old, the level of anxiety and fear was measured with two behavioural tests; an open field test and an elevated plus maze test. The Barnes platform maze was used to test spatial learning, and memory by using acquisition trials followed by reverse trial sessions. The MS24 mice spent more time in the open arms of the elevated plus maze compared to controls, but no other treatment differences were found in the emotional behavioural tests. However, in the reverse trial for the Barnes maze test there was a significant difference in the frequency of visits to the old goal, the number of errors made by the MS24 mice compared to controls and in total distance moved. The mice were subsequently sacrificed and the total number of neurons estimated in the hippocampus using the optical fractionator. We found a significant loss of neurons in the dentate gyrus in MS mice compared to controls. Apparently a single maternal separation can impact the number of neurons in mouse hippocampus either by a decrease of neurogenesis or as an increase in neuron apoptosis. This study is the first to assess the result of maternal separation combining behaviour and stereology.

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Figures

Fig. 1

Fig. 1

Three different search strategies could be applied: Random, a pattern that include many hole examinations in a random manner; Serial, a relative systematic search either clockwise or counterclockwise; Spatial, a pattern where the target box is found within relative short time and with high accuracy

Fig. 2

Fig. 2

A schematic drawing of the hippocampus with the five subregions identified in this study. Dg, the granule cell layer of the dentate gyrus; h/CA4, hilus of the dentate gyrus; ri, regio inferior; CA3/2, rs, region superior; CA1, s, subiculum

Fig. 3

Fig. 3

The mean (+SEM) time spent in both the open and closed arms. *There was a significant difference between MS 24 (N = 16) and SFR 24 (N = 5) in time spent in open arms (P < 0.05, ANOVA). ** Time spent in closed arms compared with time spent in open arms (P < 0.001, t test)

Fig. 4

Fig. 4

Left: Mean (±SEM) latency to “Goal”. There was a significant difference in Trial progress and a significant Trial x Group interaction (P < 0.05). Right: Mean (±SEM) frequency of visits to “Old Goal”. There was * a significant difference between the two groups (P < 0.05, Mann–Whitney U test) and a significant decrease over time (P < 0.05, RM ANOVA). MS 24 (N = 16) and SFR (N = 5)

Fig. 5

Fig. 5

Mean (±SEM) distance moved in reverse trials. There was a significant decrease over time (P < 0.05, RM ANOVA) and * a significant difference between the two treatment groups (P < 0.05, Mann–Whitney U test) but no significant Trial x Group interaction. MS 24 (N = 16) and SFR (N = 5)

Fig. 6

Fig. 6

Mean (±SEM) frequency of errors in MS 24 (N = 16) and SFR (N = 5) * there was a significant difference between the two treatment groups and a significant decrease in Trial progress (P < 0.05). MS 24 (N = 16) and SFR (N = 5)

Fig. 7

Fig. 7

Overview of mean (%) search strategies applied in the acquisition and reverse trial sessions. The search pattern evolved over time from a random to a serial, and finally to a spatial search strategy. From acquisition days 2 and 3, the SFR animals adopted a serial search strategy, while the MS animals maintained a random search strategy. On all other acquisition and reversal training days the two experimental groups did not differ significantly with respect to their choice of search strategy. SFR (N = 5) animals to the left and MS (N = 16) animals to the right

Fig. 8

Fig. 8

The total neuron number for the two treatment groups in five sub-regions of the mouse hippocampus for the pooled data in MS (N = 12) and SFR (N = 7). * MS ≠ SFR, P < 0.05, Student´s t test in the dentate gyrus. filled circle MS; open circle SFR; Sub Subiculum, CA 4 Hilus, DG Dentate Gyrus

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