Activation of hippocampal granule and pyramidal neurons by ambiguously conditioned cues is altered in mice lacking adult neurogenesis.

<p>(A) Confocal image of the hippocampus shows neurons that were active (Fos+, red) and inactive (blue counterstain) during fear conditioning in the dentate gyrus (DG), CA3, and CA1. (B) Two hours after the third session of tone-shock pairings, TK mice (<i>n</i> = 8) had fewer Fos+ cells than wild-type (WT) mice (<i>n</i> = 7) in the ambiguous cue condition but not the reliable cue condition (WT, TK <i>n</i> = 6, 5) across all hippocampal regions (cue type x genotype interaction F_1,22 = 6.3, <i>p</i> = 0.020; †, post hoc testing indicates <i>p</i> < 0.05 versus WT in the same condition/region). (C) Confocal image of Fos immunostaining (red) in BrdU+ (green) cell in the granule cell layer (gcl) shows a 4-wk-old granule neuron active during fear conditioning. (D) Adult-born granule neurons, labeled with BrdU, in WT mice were similarly activated by reliable (r) and ambiguous (a) cue training (t₁₀ = 1.1, <i>p</i> = 0.32); TK mice had no new neurons. (E) Confocal image of the amygdala shows Fos staining in the lateral/basolateral (LA/BLA) and central (CeA) nuclei of the amygdala. (F) The number of Fos+ LA/BLA cells was lower in the ambiguous cue condition relative to the reliable cue condition but there was no effect of genotype (main effect of predictor type F_1,22 = 5.0, <i>p</i> = 0.0363; main effect of genotype F_1,22 = 0.09, <i>p</i> = .7628; WT, TK <i>n</i> = 6, 5). No significant differences were observed across cue type or genotype in the CeA (all effects F_1,22 < 1.67, <i>p</i> > 0.2). Data are represented as mean ± standard error of the mean (SEM). The numerical data used in all figures can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2001154#pbio.2001154.s012" target="_blank">S1 Data</a>.