Irradiation impairs contextual but not cued fear conditioning. (A-C) Schematic diagram of the fear conditioning procedure (n = 14 per group). (A) Day 1: training (context A). (B) Day 2: cued test (context B). (C) Day 3: context test (context A). (D) Conditioned freezing during the tone test. Percent time freezing during the 60 s before tone presentation (pretone) and during the 20-s tone presentation (Tone). Data were subjected to a 2 (treatment) × 2 (period: pretone vs. tone) ANOVA (n = 14 per group). Mice froze significantly more during the tone than during the pretone period [F(1,26) = 38.7, P < 0.001]. There was no effect of X irradiation [F(1,26) = 0.3] and no treatment × period interaction [F(1,26) < 1]. (E) Percent time freezing during the 4 min of the context test. Data were subjected to a 2 (treatment) × 4 (minute) ANOVA. Irradiated mice spent significantly less time freezing than sham mice [F(1,26) = 5.4, P = 0.03]. Error bars represent ± 1 SEM.

Ablation of neurogenesis prevents a form of LTP in the DG. Slices for physiological experiments were derived either 3 months after x-ray treatment (A-C) or immediately after a 6-week GCV treatment was completed (D-F). (A) MPP/DG LTP in sham (n = 8) and irradiated (n = 8) mice 3 months after treatment. Arrow indicates the delivery of the 100-Hz stimulation. Repeated-measures ANOVA performed on the last 10 min of recording confirmed a significant difference between sham and x-irradiated animals [F(1,14) = 11.2, P < 0.001]. (B) LTP evoked in the DG after the addition of 50 μM picrotoxin. Stimulation parameters are the same as above. There is no difference in LTP between sham and irradiated mice [F(1,14) < 1]. (C) LTP in the Schaffer collateral to CA1 connection was not altered by irradiation [F(1,14) < 1]. (D) Six weeks of GCV treatment caused a loss of LTP in the DG in TG (n = 9) but not WT (n = 15) mice. Repeated measures ANOVA on the last 10 min confirmed a significant difference between WT and TG animals [F(1,24) = 7.2, P = 0.01]. (E) GCV treatment did not alter DG LTP elicited in the presence of 50 μM picrotoxin [F(1,24) < 1]. (F) LTP in Schaffer collateral/CA1 connections was also unaffected by GCV [F(1,24) < 1]. Error bars represent ± 1 SEM.

GCV treatment impairs contextual but not cued fear conditioning in GFAP-TK TG mice. (A) Conditioned freezing during the tone test. Percent of time freezing during the 60 s before tone presentation (pretone) and during the 20-s tone presentation (tone) is shown. Data were subjected to a 2 (treatment) × 2 (period: pretone vs. tone) ANOVA [n = 19 (WT) and 11 (TG)]. Mice froze significantly more during the tone than during the pretone period [F(1,28) = 14.1, P < 0.001]. There was no effect of genotype [F(1,28) = 0.5] or genotype × period interaction [F(1,28) < 1]. (B) Percent time freezing during the 4 min of the context test. Data were subjected to a 2 (treatment) × 4 (minute) ANOVA. Irradiated mice spent significantly less time freezing than did sham mice [F(1,28) = 4.7, P = 0.04].