Figure 5. Microglial TNFα required for... | Rockefeller University Press

$Microglial TNFα required for memory consolidation in sleep-dependent learning tasks. (a) Experimental design: Mice learn to run on the complex wheel (session 1, S1) and consolidation of memory is tested the following day (session 2, S2). Between S1 and S2, mice are left undisturbed in their cages. (b) Average latency to fall off the complex wheel in the first three and the last three trials of S1 and S2 from tCTL and micTNFα-KO. Gray area represents undisturbed sleep–wake cycle. Dashed line represents S1 to S2 consolidation. 8 tCTL and 10 micTNFα-KO mice. The data represent mean ± SEM. (c) Improvement within each session was measured as the ratio between the mean of the best three trials and first three trials. No statistical significance (ns) by unpaired two-tailed Mann–Whitney test. (d) Performance improvement across sessions was measured as the ratio between the mean of S2 and S1 trials. *P < 0.05, unpaired two-tailed Mann–Whitney test. (e) Consolidation of motor learning across sessions was measured in two ways: the ratio between the mean of the first three trials of S2 and mean of the last three trials of S1 (first S2/last S1) or ratio between mean of first three trials of S2 and mean of S1 trials (first S2/mean S1). *P < 0.05 and **P < 0.01, unpaired two-tailed Mann–Whitney test. (c–e) 8 tCTL and 10 micTNFα-KO mice. Results are presented as minimum to maximum box-plots with the individual values of each mouse represented as datapoints. (f and h) Novelty preference in the novel floor-texture recognition (FTR) (f) or the Novel Object Recognition (NOR) task (h). Fractional preference is expressed as a function of cumulative time of exploration (see Materials and methods). The data represent the mean ± SEM of the preference for the object placed on the novel floor texture (f) or for the novel object (h) computed for each animal. #P < 0.05, ##P < 0.01, and ###P < 0.001 preference for one object versus no preference and *P < 0.05, **P < 0.01, and ***P < 0.001 CTL versus micTNFα-KO. Unpaired t tests. The fractional preference is equal to 1 or −1 when the animal only explored respectively the object placed on the novel or familiar floor texture in the FTR and the novel or familiar object in the NOR, and 0 when the animal spent exactly the same amount of time on the two objects. (g and i) Total duration of exploration of the novel floor (FTR; g) and of the novel object (NOR; i). Boxes represent quartiles and whiskers correspond to the range of data; points are singled as outliers if they deviate more than 1.5 × inter-quartile range from the nearest quartile. (g) °P = 0.0674 CTL versus micTNFα-KO, Unpaired t tests. (i) P = 0.44 CTL versus. micTNFα-KO. Unpaired t tests; (f–i) n = 11 tCTL and 8 (f and g) or 16 (h and i) micTNFα-KO mice.$

Figure 5.

Microglial TNFα required for memory consolidation in sleep-dependent learning tasks. (a) Experimental design: Mice learn to run on the complex wheel (session 1, S1) and consolidation of memory is tested the following day (session 2, S2). Between S1 and S2, mice are left undisturbed in their cages. (b) Average latency to fall off the complex wheel in the first three and the last three trials of S1 and S2 from tCTL and micTNFα-KO. Gray area represents undisturbed sleep–wake cycle. Dashed line represents S1 to S2 consolidation. 8 tCTL and 10 micTNFα-KO mice. The data represent mean ± SEM. (c) Improvement within each session was measured as the ratio between the mean of the best three trials and first three trials. No statistical significance (ns) by unpaired two-tailed Mann–Whitney test. (d) Performance improvement across sessions was measured as the ratio between the mean of S2 and S1 trials. *P < 0.05, unpaired two-tailed Mann–Whitney test. (e) Consolidation of motor learning across sessions was measured in two ways: the ratio between the mean of the first three trials of S2 and mean of the last three trials of S1 (first S2/last S1) or ratio between mean of first three trials of S2 and mean of S1 trials (first S2/mean S1). *P < 0.05 and **P < 0.01, unpaired two-tailed Mann–Whitney test. (c–e) 8 tCTL and 10 micTNFα-KO mice. Results are presented as minimum to maximum box-plots with the individual values of each mouse represented as datapoints. (f and h) Novelty preference in the novel floor-texture recognition (FTR) (f) or the Novel Object Recognition (NOR) task (h). Fractional preference is expressed as a function of cumulative time of exploration (see Materials and methods). The data represent the mean ± SEM of the preference for the object placed on the novel floor texture (f) or for the novel object (h) computed for each animal. ^#P < 0.05, ^##P < 0.01, and ^###P < 0.001 preference for one object versus no preference and *P < 0.05, **P < 0.01, and ***P < 0.001 CTL versus micTNFα-KO. Unpaired t tests. The fractional preference is equal to 1 or −1 when the animal only explored respectively the object placed on the novel or familiar floor texture in the FTR and the novel or familiar object in the NOR, and 0 when the animal spent exactly the same amount of time on the two objects. (g and i) Total duration of exploration of the novel floor (FTR; g) and of the novel object (NOR; i). Boxes represent quartiles and whiskers correspond to the range of data; points are singled as outliers if they deviate more than 1.5 × inter-quartile range from the nearest quartile. (g) °P = 0.0674 CTL versus micTNFα-KO, Unpaired t tests. (i) P = 0.44 CTL versus. micTNFα-KO. Unpaired t tests; (f–i) n = 11 tCTL and 8 (f and g) or 16 (h and i) micTNFα-KO mice.

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