Figure 4.

Chronic glucocorticoid exposure causes spine loss and memory impairment. (a) Experimental procedure. (b) Prolonged corticosterone (cort) exposure disrupted the survival of learning-related spines that were present for at least 1 week (F_1,5 = 54.2, P < 0.001). New spine survival represents the number of spines formed during the 2-d training period and persisting on day 20, expressed as a percentage of the total number of spines at baseline. (c) Prolonged cort exposure was associated with corresponding deficits in retention of the motor skill (F_1,16 = 42.2, P < 0.001). (d) Elimination rates for spines present before training also increased (F_1,5 = 66.6, P < 0.001). Elimination rates describe the number of spines that were present before training (day 0) and eliminated on day 20, expressed as a percentage of the total number of spines at baseline. (e) Chronic cort (F_1,5 = 125.9, P < 0.001) but not transient cort or learning (F_4,19 = 2.07, P = 0.13), caused significant spine loss. Net change in spine number represents the combined effects of elimination and formation on total spine number, relative to the small (4–5%) rate of net spine loss observed in untrained controls (ctrl). (f) The survival of new spines formed during training was strongly correlated with the elimination of pre-existing spines (r = 0.91, P < 0.001), but this balance was disrupted after chronic cort exposure (red). *P < 0.05 (corrected) versus vehicle-treated control. Error bars, s.e.m. See Supplementary Table 4 for statistics and details.