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. 2022 Feb 3;13:680. doi: 10.1038/s41467-022-28301-z

Fig. 8. Autophagy deficiency in excitatory neurons alters cognitive flexibility.

Fig. 8

a Survival plot of discrimination learning (DL) indicating the total number of entries in the cognition wall till the 80% learning criterion for atg5f/f and thy1-cKO animals. Each vertical segment of the curve represents a mouse that reached the criterion at the represented number of entries on the x-axis (N = 11 animals per genotype). Statistical analysis was performed using log-rank (Mantel-Cox) test (P = 0.5354). b Survival plot of reversal learning (RL) indicating the total number of entries in the cognition wall till the 80% reversal-learning criterion for atg5f/f and thy1-cKO animals. Each vertical segment of the curve represents a mouse that reached the criterion at the represented number of entries on the x-axis (N = 11 animals per genotype). Statistical analysis was performed using log-rank (Mantel-Cox) test (P = 0.0472). c Graph showing the total entries from all entrances of the cognition wall during the RL phase between atg5f/f and thy1-cKO animals (N = 11 animals per genotype). Statistical analysis was performed by unpaired, two-tailed Student’s t-test (P = 0.012). d Graph showing the total distance moved in meters during both DL and RL of atg5f/f and thy1-cKO animals (N = 11 animals per genotype). Statistical analysis was performed by unpaired, two-tailed Student’s t-test (P = 0.6912). e Same as in a, survival plot of DL for atg5f/f and thy1-cKO animals with administration of TAT-GluR23Y or TAT-GluR23A in the following two days of the experiment (N = 13 animals per genotype and treatment). Statistical analysis was performed using log-rank (Mantel-Cox) (for thy1-cKO animals PGluR23Y_GluR23A = 0.1163; for atg5f/f animals PGluR23Y_GluR23A = 0.00002). f Same as in b survival plot of RL among atg5f/f and thy1-cKO animals with administration of TAT-GluR23Y or TAT-GluR23A, 1 h before RL on day 3 and 4 of the experiment (N = 13 animals per genotype and treatment). Statistical analysis was performed using log-rank (Mantel-Cox) (for thy1-cKO animals PGluR23Y_GluR23A = 0.5549, for atg5f/f animals PGluR23Y_GluR23A = 0.0740). g Same as in c, for atg5f/f and thy1-cKO animals with administration of TAT-GluR23Y or TAT-GluR23A (N = 13 per genotype and treatment). Bars represent mean values ± SEM. Statistical analyses were performed by one-way ANOVA ((F3,48) = 2.220, P = 0.0979) (Tukey’s test Patg5f/f/TAT-GluR23A-thy1cKOTAT-GluR23A = 0.2042, Patg5f/f/TAT-Glu23A-atg5f/f/TAT-GluR23Y = 0.8198, Patg5f/f/TAT-GluR23A-thy1cKOTAT-GluR23Y = 0.9816, Pthy1cKOTAT-GluR23A-atg5f/f/TAT-GluR23Y = 0.6768, Pthy1cKOTAT-GluR23A-thy1cKO/TAT-GluR23Y = 0.0965, Patg5f/f/TAT-GluR23Y-thy1cKOTAT-GluR23Y = 0.6004). h same as in d, for atg5f/f and thy1-cKO animals with administration of TAT-GluR23Y or TAT-GluR23A (N = 13 animals per genotype and treatment). Bars represent mean values ± SEM. Statistical analyses were performed by one-way ANOVA ((F3,48) = 0.6423, P = 0.5916) (Tukey’s test Patg5f/f/TAT-GluR23A-thy1cKOTAT-GluR23A = 0.9492, Patg5f/f/TAT-GluR23A-atg5f/f/TAT-GluR23Y = 0.5819, Patg5f/f/TAT-GluR23A-thy1cKOTAT-GluR23Y = 0.7271, Pthy1cKO/TAT-GluR23A-atg5f/f/TAT-GluR23Y = 0.8810, Pthy1cKOTAT-GluR23A-thy1cKOTAT-GluR23Y = 0.9583, Patg5f/f/TAT-GluR23Y-thy1cKOTAT-GluR23Y = 0.9952).