Midday meals do not impair mouse memory

Abstract

Nocturnal mice fed in the middle of the light period exhibit food anticipatory rhythms of behavior and physiology under control of food-entrainable circadian clocks in the brain and body. This is presumed to be adaptive by aligning behavior and physiology with predictable mealtimes. This assumption is challenged by a report that daytime feeding schedules impair cognitive processes important for survival, including object memory and contextual fear conditioning assessed at two times of day. To further evaluate these effects, mice were restricted to a 6 h daily meal in the middle of the light or dark period and object memory was tested at four times of day. Object memory was not impaired by daytime feeding, and did not exhibit circadian variation in either group. To determine whether impairment might depend on methodology, experimental procedures used previously to detect impairment were followed. Daytime feeding induced food anticipatory rhythms and shifted hippocampal clock genes, but again did not impair object memory. Spontaneous alternation and contextual fear conditioning were also not impaired. Hippocampal memory function appears more robust to time of day and daytime feeding schedules than previously reported; day-fed mice can remember what they have seen, where they have been, and where it is dangerous.

Figure 1

Effects of feeding schedules and time of day on test performance. (A) Experiment 1. Discrimination Index (DI, time spent exploring the novel object as a percentage of time spent exploring both objects) scores on novel object recognition (NOR) test in a Y-maze. Chance level is 0.5 (red dotted line). (B) Experiment 2. DI scores on NOR test in an open field. (C) Experiment 3a. Alternation percentages in a Y-maze. Chance level is 50% (red dotted line). (D) Experiment 3b. Freezing % in shock box, 24 h after receiving foot shock.

Figure 2

Effects of feeding schedules and time of day on locomotor activity in (A) day-fed and (B) night-fed mice in Experiment 1. Activity data for individual mice were first normalized and then averaged across the last 5 days of restricted feeding prior to habituation sessions. Day- and night-tested subgroups were pooled. Group means are plotted ± SEM. Mealtimes are denoted by green shading.

Figure 3

Effects of feeding schedules and time of day on clock gene expression in the hippocampus. A. Per2. B. Bmal1. Data are plotted as mean ± SEM (N = 3–5 mice per time point, per feeding condition; ZT3 is double-plotted to aid visualization). Red circles and lines are day-fed groups. Black squares and lines are night-fed groups. There was a significant main effect of time of day in both groups and a significant interaction between time of day and feeding condition (****p < 0.0001).