DA-Tsc1-KO mice exhibit reduced cognitive flexibility. a Schematic of the four-choice odor-based reversal learning task. Orange ring denotes the food reward. Dark blue circle in Reversal indicates a novel odor. b, c Mean ± SEM number of trials taken to reach criterion (eight out of ten correct) during acquisition learning (b) and total errors made during acquisition learning (c) in the four-choice test. d Step function cumulative reward plot for individual animals during acquisition learning. e, f Mean ± SEM number of trials taken to reach criterion (eight out of ten correct) during reversal learning (e, *p = 0.0392) and total errors made during reversal learning (f, *p = 0.0230), unpaired, two-tailed t tests. g Step function cumulative reward plot for individual animals during reversal learning. h Analysis of different error types during reversal learning. Bars represent mean ± SEM number of perseverative (Pers.), regressive (Reg.), novel, irrelevant (Irrel.), or omission (Omis.) errors for mice of each genotype. Two-way ANOVA p values are shown. ****p < 0.0001, Sidak’s multiple comparisons test. i Mean ± SEM total number of rewards obtained and consumed during acquisition (Acq.) and reversal (Rev.) learning. j Mean ± SEM and number of trials to reach criterion (eight out of ten correct) during reversal learning after the first correct selection of the newly rewarded odor. k Mean ± SEM number of odor selections in bins of 4 trials during reversal learning. Odor 1 is the odor rewarded during acquisition learning and odor 2 is the odor rewarded during reversal learning. For all panels DA-Tsc1-WT: n = 8 male mice and DA-Tsc1-KO: n = 10 male mice. For all bar graphs, dots represent values for individual mice. See Supplementary Table 5 for p values for all behavior tests. Source data are provided as a Source Data file.