Fig. 1: Instrumental reward learning is age-dependently impaired in 3xTg mice.

a Schematic of procedure used for operant self-administration of palatable food pellets. b 3xTg mice acquired operant self-administration of palatable pellets more slowly than WT mice (main effect, P = 0.0106, F1,52 = 7.034) with the greatest effect between genotypes at 12-mo (two-tailed Sidak’s multiple comparison, P = 0.0003). c Raster plots showing correct side nose poke responding (vertical ticks along the x-axis) on day 1 of training for individual mice (by row) that eventually acquired self-administration. While there was considerable variation within the 3xTg groups, overall they showed less responding on day 1 compared to WT mice. d–g Representative locomotor data from individual 3- and 12-mo WT and 3xTg mice during the first thirty minutes in the chamber, stratified by time (tornado plots) and heatmap localization (residency plots). h 3xTg mice locomote significantly more than WT mice over the 1-h session (two-way ANOVA, main effect of genotype, P = 0.0006, F1,38 = 13.84, n = 42 mice) which was most dramatic at 3 mo (P = 0.0018, two-tailed Sidak’s). i 3xTg mice spent significantly more time in the center of the chamber during the 1-h session than WT mice (two-way ANOVA, main effect of genotype, P = 0.0365, F = 1,38 = 4.699, same animals as in h). Residency plot scalebars represent log-transformed data rescaled between minimum and maximum values. Error bars represent standard error. Source data are provided as a Source Data file. Created in BioRender. Beckstead, M. (2023) BioRender.com/p21u763.