Supplementary Figure 8: Sphk2–/– mice show decreased fear extinction in the contextual fear paradigm. | Nature Neuroscience

Supplementary Figure 8: Sphk2–/– mice show decreased fear extinction in the contextual fear paradigm.

From: Active, phosphorylated fingolimod inhibits histone deacetylases and facilitates fear extinction memory

Supplementary Figure 8

(a) SphK2-/- and WT mice do not forget the association between the context and footshock 48 h after conditioning. Mice were subjected to three footshocks on the conditioning day and received a 2.5 min test 48 h later. SphK2-/- and WT mice exhibited similar levels of freezing pre-shock, post-shock, and 48 h after conditioning (i.e., no extinction sessions) (two-way repeated-measures ANOVA; interaction: F(2,30) = 0.77; P = 0.47; time: F(2,30) = 100.95; P < 0.0001; genotype: F(1,30) = 0.87; P = 0.37). Percent time freezing in both genotypes was significantly increased post-shock and at 48 h compared to pre-shock (*P < 0.001, Bonferroni post hoc test). N = 8 for WT; N =9 for SphK2-/- mice. (b) SphK2-/- mice display extinction learning deficits in the contextual fear paradigm. SphK2-/- and WT mice were subjected to three footshocks on day 1 and received one extinction session (10 min) 24 h later (E1, consecutive 2.5 min bins are indicated by 1, 2, 3, 4). Mice were then evaluated on day 3 in a 2.5 min test. Both genotypes exhibited similar levels of freezing pre-shock, post-shock, and 24 h after conditioning (two-way repeated-measures ANOVA; interaction: F(2,32) = 1.44; P = 0.26; time: F(2,32) = 110; P < 0.0001; genotype: F(1,32) = 1.87; P = 0.19). Significant increases in freezing were found post-shock (P < 0.001) and in the first 2.5 min bin of the extinction session (E1) (P < 0.001) as compared with pre-shock levels of freezing (Bonferroni post hoc test). In the 10 min extinction session both genotypes exhibited similar freezing behavior (two-way repeated measures ANOVA; interaction: F(3,48) = 2.01; p = 0.13); extinction time: F(3,48) = 6.22; P < 0.0012; genotype: F(1,48) = 1.6; P = 0.22). # P < 0.01 indicates a significant difference from the first bin of the extinction session for both genotypes (Bonferroni post hoc test), †P < 0.05 indicates a significant difference between WT and SphK2-/- mice on test day 3 (Bonferroni post hoc test). N = 9 per group. Data are presented as mean ± s.e.m.

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