Fig. 2: Tcf4 gene-dosage modulates cognition in environment-dependent manner. | Translational Psychiatry

Fig. 2: Tcf4 gene-dosage modulates cognition in environment-dependent manner.

From: Modulation of cognition and neuronal plasticity in gain- and loss-of-function mouse models of the schizophrenia risk gene Tcf4

Fig. 2

Tcf4tg mice (cohort 1, a, b; cohort 2, d, e) and Tcf4Ex4δ+/− mice (cohort 3, g, h) were submitted to spatial learning in the water maze task. Cumulated results from water maze and other behavioral profiling (Table 1) are depicted as radar charts for Tcf4tg (c, f) and Tcf4Ex4δ+/− (i) mice. a In the initial learning task in Morris Water Maze, Tcf4tg and wt mice in isolation rearing (IR) learned slower than mice in enriched environment (EE) (p < 0.001, environmental effect), as measured by the latency to reach a hidden platform. The effect was independent of genotype (p = 0.210, G×E interaction test). b During reversal learning, Tcf4tg mice subjected to IR needed more time to reach the platform than IR subjected wt littermates (p = 0.005), indicating an impairment of cognitive flexibility. c Behavioral profiles show impaired spatial learning upon IR (blue) and no cognitive deficits upon EE (green) in Tcf4tg mice compared to wt mice from the corresponding environment (black). Green and blue stars indicate significant differences (see Table 1 and Dataset Supplementary Fig. 1 for details) between Tcf4tg EE (green) vs. reference (wt EE, black) and between Tcf4tg IR (blue) and reference (wt IR, black), respectively. IR significantly impaired cognition in Tcf4tg mice (cognitive symptom class: p = 0.005, cognitive domain flexibility learning: p = 0.005, cognitive trait cue memory: p = 0.001; all passing multiple-tesing correction). However, at the superdomain level displayed here, only nominal significance was reached (spatial learning p = 0.019, fear memory p = 0.044, blue stars in brackets). d During initial learning, socially defeated (SD) Tcf4tg mice displayed longer platform latencies than mutants from the handling control (HC) group or wt animals (p ≤ 0.001). Tcf4tg HC mice showed slightly delayed platform latencies than wt HC animals (p = 0.007, not reaching significance after Bonferroni correction). e In reversal learning (i.e. flexibility learning), Tcf4tg mice needed significantly more time to reach the platform than wt animals in both SD (p < 0.001) and HC groups (p = 0.002). f Behavioral profiles of Tcf4tg mice from SD and HC. Spatial learning in Tcf4tg mice is significantly impaired upon SD (red) and mildly in HC (gray) compared to wt mice in the corresponding conditions (black) as indicated by stars of corresponding colors (multiple-testing adjusted significance, see Table 1 and Dataset Supplementary Fig. 1 for details). Pain sensitivity was not assessed in this cohort (as indicated by white circle). g, h Tcf4Ex4δ+/− mice housed in IR displayed higher platform latencies than wt controls in initial learning (p < 0.001)(g) and flexibility learning (p < 0.001)(h). i Behavioral profiles of Tcf4Ex4δ+/− mice (blue) show that spatial learning and working memory are impaired compared to wt mice (black), as indicated by blue stars (multiple-testing adjusted significance, see Table 1 and Supplementary Table 1 for details). a, b, d, e, g, h Data represent mean ± SEM. n = 12–16 mice per genotype and housing conditions. See Table 1 and Dataset Supplementary Fig. 1 for detailed statistics.

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