Chronic stress enhances spatial memory in ovariectomized female rats despite CA3 dendritic retraction: possible involvement of CA1 neurons

Abstract

Emerging data report sex differences in how the brain responds to chronic stress. Here, we investigated the effects of chronic restraint stress (6 h/day/21 days) on hippocampal morphology and function in ovariectomized female rats. Chronic restraint stress caused CA3 apical dendritic retraction in short- and long-shafted neurons, while it reduced basal dendritic arbors in long-shafted neurons only. Chronic restraint did not affect CA1 dendritic arborization, although it increased the proportion of CA1 spine heads compared with controls. Both stressed and control animals performed well on the Y-maze, a spatial memory task. However, chronic stress enhanced Y-maze performance compared with controls, which may reflect facilitated spatial memory or reduced habituation. Y-maze performance correlated with CA1 spine head proportion. This relationship suggests that spatial ability in females may be more tightly coupled with CA1 morphology, which may override the influence of CA3 dendritic retraction. Thus, this research provides additional evidence that CA3 morphology does not always parallel spatial memory.

Fig. 1

Golgi-Stained CA3 Neurons. Camera lucida drawings (320×) represent experimental conditions of the two CA3 neuronal types studied. (A) Control SS, (B) Stress SS, (C) Control LS, and (D) Stress LS. Note the reduction in apical dendritic complexity in the stressed (B, D) vs. control neurons (A, C). Basal dendritic retraction was evident in the LS stressed group only (D) compared with LS control neurons (C).

Fig. 2

CA3 apical and basal dendritic morphology. Chronic restraint decreased both the apical branch points (A) and branch length (B). In addition, SS cells had more apical branch points and overall apical branch length compared with LS cells for both stressed and control conditions. Chronic restraint reduced both LS basal branch points (C) and length (D) compared with SS branch points and length. Data points represent group means ± S.E.M. * P<0.05 stress vs control. + P<0.05 SS vs. LS. For basal data, statistical significance is indicated by means with different letters (n=12 rats/group).

Fig. 3

Basal CA1 dendritic spine proportions (heads to total). (A) Camera lucida drawings (1250×) represent CA1 basal dendritic spines from control and stress groups. The closed arrow points to an example of a headless spine whereas the open arrow points to a spine head. (B) Stressed rats had significantly more basal dendritic spines with heads compared with controls. Data points represent group means ± S.E.M. * P<0.05 (n = 10 rats/group).

Fig. 4

Influence of chronic stress on Y-maze performance. (A) Both groups entered the novel arm more than the other arm, * P<0.05 Novel vs. Other. (B) Stressed rats had significantly greater positive difference scores compared with control rats, * P<0.05, stress vs. control. Data points represent group means ± S.E.M. (control n = 39, stress n = 38).

Fig. 5

Correlation between Y-maze difference scores and proportion of CA1 basal spine heads. There was a significant, positive relationship for greater difference scores on the Y-maze (i.e. preference for the novel arm) to be associated with higher proportions of CA1 dendritic spines with heads, r_s(8) = .54, P<0.05 (n = 10 rats/group).