Fig. 6. Prefrontal spinogenesis sustains antidepressant-induced behavioral recovery over time.
(A) Experimental time course schematic. To control for individual differences in TST behavior as in a recently published report (72), we tested subjects before chronic CORT exposure and again 2 days after ketamine treatment (Rx) to determine whether ketamine reversed CORT effects on immobility and whether maintaining this effect required spine formation. (B) Photoactivating AS-PaRac1 (N = 7 mice) blocked ketamine effects on spine formation (Wilcoxon W = 50.0, *P = 0.0025) (right) and increased spine elimination (Wilcoxon W = 18.0, *P = 0.0177) (left) compared with that in controls not expressing AS-PaRac1 (N = 5 mice). (C) Photoactivating AS-PaRac1 interfered with the maintenance of ketamine’s effects on immobility behavior (F1,17 = 9.96, *P = 0.0058) and (D) calcium-transient frequency (F1,17 = 16.6, *P = 0.019) during tail suspension 2 days after treatment. (E) No effect of photoactivating AS-PaRac1 on sucrose preference behavior 2 days after ketamine treatment (N = 8 mice per group; Wilcoxon W = 63.0, P = 0.645). (F) Photoactivating AS-PaRac1 3 hours after ketamine treatment (before the onset of ketamine’s effects on spine formation) had no effect on TST behavior 2 days after treatment (F1,17 = 0.201, P = 0.660, N = 10 AsPaRac1 mice and N = 9 controls). NS, not significant.