Circadian rhythm of female WT and IL-1R1^−/− mice.

<p>The activity of female WT (n = 15) and female IL-1R1^−/− (n = 15) mice was recorded using the Phenotyper home cage over a period of three nights and two days. Data are plotted in 4 hour blocks and are expressed as mean±SEM and were analysed by two way repeated measures ANOVA with strain as between subjects factor and time as within subjects factor. There was no effect of strain but a significant time × strain interaction, which is denoted by *p<0.0003.</p

Cytokine and chemokine transcription and synthesis.

<p>Cytokine and chemokine transcription and synthesis.</p

Ventricular volume and synaptic density in WT and IL-1R1^−/− mice.

<p>(a–c) Representative images of the hippocampus and lateral ventricle of WT (a) and IL-1R1^−/− (b) brain. Ventricular volume in WT (n = 4) and IL-1R1^−/− mice (n = 6) was assessed using Image J Software (c). Areas were calculated for sections from each animal at 2.0 and 2.3 mm posterior to Bregma and summed and multiplied by the summed section thickness (2×10 µm: 0.02 mm). Data are non-parametric and have been presented as dot plots with median value denoted by the bar. (d–i) Synaptophysin labelling in the dorsal (see inset *) and more ventral hippocampus (approximately −3.0 mm from surface of brain; see inset *) of WT (d, g) and IL-1R1^−/− mice (e, h). Synaptic density analysis of the dorsal hippocampus: ratio of stratum radiatum to dentate gyrus molecular (f) and ventral hippocampus ratio of stratum radiatum to stratum lacunosum moleculare (i) for WT (n = 4) and IL-1R1^−/− (n = 5).</p

Spatial and non-spatial memory in the Morris water maze in IL-1R1^−/− and WT mice.

<p>(a) The latency to reach the hidden platform, and (b) the path length were assessed in IL-1R1^−/− mice (n = 11) and WT mice (n = 20) in the spatial memory water maze task across 9 trials with 1 hour inter trial interval. (c) Probe trials performed after 9 trials and 27 trials (dotted line shows 25%), and (d) non-spatial memory (flag trial) in IL-1R1^−/− mice and WT. Data are expressed as mean±SEM and were analysed by two-way repeated-measures ANOVA with strain as between subjects factor and time as within subjects factor (a, b) or by t-test (c, d). * denotes main effect of strain (p = 0.02).</p

Performance of IL-1R1^−/− mice versus WT in the contextual fear conditioning paradigm.

<p>The time spent freezing measured across 2 minutes (pre-shock) and 5 minutes, 48 hours later (post shock), following foot shock at 0.4 mA for 2 seconds for IL-1R1^−/− mice (n = 10) and WT mice (n = 10) in the fear conditioning paradigm. Data are expressed as mean±SEM and were analysed by t-test, bars representing pre-shock freezing are insufficiently large to be clearly visible. Bonferroni post-hoc tests after a significant effect of treatment in ANOVA analysis showed that both strains showed significant differences from their pre-shock freezing (***p<0.001).</p

Open field and elevated plus maze activity in IL-1R1^−/− and WT mice.

<p>(a) Distance travelled in open field in IL-1R1^−/− mice (n = 11) compared to WT (n = 19) and (b) the number of rears recorded in open field, across 3 minutes. (c) The time spent in open arms of elevated plus maze and (d) the latency to first emerge from closed arm. Data are expressed as mean ± SEM and significant differences by t -test are denoted by ***p<0.0001 and *p<0.05.</p

Spatial memory and choice performance on the spatial-discrimination beacon water maze task in IL-1R1^−/− and WT mice.

<p>IL-1R1^−/− and WT mice (n = 10) were trained (8 trials per day for 12 days) to discriminate between two identical beacons (diameter 15 cm; 24 cm high, sitting on the water surface) depending on their spatial locations, one of which had a hidden platform underneath. 1 block = 24 trials. a) First choice accuracy to choose the correct beacon was assessed. b) Probe test performed after 72 trials, with 25% depicted by dotted line. The percentage correct choices on choosing the correct beacon are shown when start position is c) close to correct beacon, d) equal distance from both beacons and e) furthest from correct beacon. * p<0.05 by one-tailed t-test comparison of first choice accuracy across all trials. Data are expressed as mean±SEM and full statistical analysis is described in the text.</p

Performance of IL-1R1^−/− mice versus WT on a visuo-spatial reference memory task and a working memory task.

<p>(a) Visuo-spatial reference memory was assessed using the Y-maze across 20 trials (5 trials per trial block) in IL-1R1^−/− (n = 11) compared to WT mice (n = 20). (b) Working memory was assessed in 1L-1R1^−/− (n = 11) and WT (n = 15) by T-maze alternation, over 12 days, 10 trials per day with block 1 representing performance of mice on days 1–4, block 2 the performance of mice on days 5–8 and block 3 the performance of mice on days 9–12. Data are shown as mean±SEM and were analysed by two-way repeated-measures ANOVA with strain as between subjects factor and trial block as within subjects factor. Main effects of trial block for both mazes are depicted by ***p<0.001.</p

Performance of male IL-1R1^−/− mice versus male WT on a battery of tasks.

<p>(a) Visuo-spatial reference memory was assessed using the Y-maze across 20 trials (n = 5 per trial block) in male IL-1R1^−/− (n = 11) compared to male WT mice (n = 9). (b) The time spent freezing before (too small to be clearly visible), and 48 hours following, 0.4 mA foot shock for male IL-1R1^−/− mice and WT mice in the fear conditioning paradigm. (c) The number of squares crossed in 3 minutes in the open field and (d) the number of rears recorded in open field, across 3 minutes (e) the time spent in open arms of the elevated plus maze and (f) entries into open arms as a proportion of total arm entries (for male and females combined). Data are expressed as mean ± SEM and figure (a, b) were analysed by two way repeated-measures ANOVA with strain as between subjects factor and time/block as within subjects factor and all other figures were analysed by one-tailed t-test and significant differences are denoted by ** p<0.001 and *p<0.05.</p