Fig. 5

Scn2a^KO/+ mice display enhanced fear memory consolidation, deficient fear extinction, and increased gamma activity in the prefrontal cortex. a Mice were conditioned using three CS-US pairs leading to a significant increase in freezing behavior at every consecutive trial. On the third exposition, the freezing percentage was however significantly higher in the Scn2a^KO/+ group (genotype-time interaction: F_2,19 = 8.708, p < 0.01). b After 24 h, successive exposition to the CS without US rapidly led to a decrease in the freezing percentage of WT mice, whereas freezing ratio remained significantly higher in Scn2a^KO/+ mice and only started to decay after seven consecutive exposition to the tone stimulus (genotype-time interaction: F_21,209 = 1.541, NS; time effect: F_21,231 = 5.096, p < 0.001; genotype effect: F_1,11 = 20.580, p < 0.001). c For further investigation of the fear extinction, the first 3 min of habituation (Pre) were used as a “freezing percentage reference” and freezing during each tone was analyzed in regards to this reference value. In WT (+/+) mice, freezing was significantly increased during the first two tones and decreased to a level that was not significantly different from the habituation period from the third tone. In Scn2a^KO/+ mice, the freezing rate remained significantly higher than the reference level from tone 1 through 6 and decreased to a level that was not significantly different from the habituation period from the tone 7. d Power spectrum densities from electrocorticogram and local field potential traces suggested a slight increase in power in the medial prefrontal cortex and the amygdala of Scn2a^KO/+ mice. Traces from other brain regions were comparable between Scn2a^KO/+ and WT samples. e The power in the gamma band (30–80 Hz) was significantly increased in the prefrontal cortex of Scn2a^KO/+ mice but not in other regions of the brain. CS conditioned stimulus, US unconditioned stimulus, ECoG electrocorticogram, mPFC medial prefrontal cortex, CPu caudate putamen, Amg basolateral amygdala, CA1 hippocampal CA1 region, Thal ventroposterior thalamus, VC visual cortex. Fear memory extinction: WT: N = 11, KO: N = 12; power spectrum densities: WT: N = 4, KO: N = 4. Values are expressed as mean ± standard error of the mean. Statistical significance was assessed using two-way repeated measures ANOVA followed by Sidak’s multiple comparison post-hoc test (a, b) or Student t test (c–e) with significance set at *p < 0.05, **p < 0.01, and ***p < 0.001