Sleep deprivation selectively impairs memory consolidation for contextual fear conditioning

Abstract

Many behavioral and electrophysiological studies in animals and humans have suggested that sleep and circadian rhythms influence memory consolidation. In rodents, hippocampus-dependent memory may be particularly sensitive to sleep deprivation after training, as spatial memory in the Morris water maze is impaired by rapid eye movement sleep deprivation following training. Spatial learning in the Morris water maze, however, requires multiple training trials and performance, as measured by time to reach the hidden platform is influenced by not only spatial learning but also procedural learning. To determine if sleep is important for the consolidation of a single-trial, hippocampus-dependent task, we sleep deprived animals for 0-5 and 5-10 h after training for contextual and cued fear conditioning. We found that sleep deprivation from 0-5 h after training for this task impaired memory consolidation for contextual fear conditioning whereas sleep deprivation from 5-10 h after training had no effect. Sleep deprivation at either time point had no effect on cued fear conditioning, a hippocampus-independent task. Previous studies have determined that memory consolidation for fear conditioning is impaired when protein kinase A and protein synthesis inhibitors are administered at the same time as when sleep deprivation is effective, suggesting that sleep deprivation may act by modifying these molecular mechanisms of memory storage.

Figure 1

Total sleep deprivation from 0–5 h after training selectively impairs memory for contextual conditioning. (A) Mice sleep deprived from 0–5 h after training freeze less in response to the shocked context than do nonsleep-deprived mice (context; P < .05; n = 21 per group). Sleep-deprived mice did not differ from nonsleep-deprived mice in freezing in the altered chamber (preconditioned stimulus [pre CS]) or in freezing in response to the noise cue (conditioned stimulus [CS]; P > .05; n = 15 per group). (B) Mice show a deficit in the specificity of freezing to the shocked context when sleep deprived from 0–5 h after training for fear conditioning. Specificity of freezing to the shocked context (delta context) measured by the difference in percent freezing between the shocked and altered context was significantly less in mice that were sleep deprived from 0–5 h after training than in nonsleep-deprived mice (P < 0.01; n = 15 per group). Cue-specific freezing (delta cue) is not altered by sleep deprivation from 0–5 h after training (P > .05; n = 15 per group). *, P < .05.

Figure 2

Order of testing does not affect impairments in memory for contextual conditioning as a result of 0–5 h of total sleep deprivation after training. Mice were trained similarly to the experiment shown in Figure 1, however, freezing in response to the conditioned stimulus (CS) in an altered context was tested at 24 h following training before freezing in response to the shocked context was tested. (A) Mice sleep deprived from 0–5 h after training freeze less in response to the shocked context than do nonsleep-deprived mice (context; P < .05; n = 9 per group). Sleep-deprived mice did not significantly differ from nonsleep-deprived mice in freezing in the altered chamber (pre CS) or in freezing in response to the cue (CS; P's > .05; n = 9 per group). (B) Mice show a deficit in the specificity of freezing to the shocked context when sleep deprived from 0–5 h after training. Specificity of freezing to the shocked context (delta context) measured by the difference in percent freezing between the shocked and altered context was significantly less in mice that were sleep deprived from 0–5 h after training than in nonsleep-deprived mice (P < .01; n = 9 per group). Cue-specific freezing (delta cue) is not altered by sleep deprivation from 0–5 h after training (P > .05; n = 15 per group). *, P < .05.

Figure 3

Total sleep deprivation from 0–5 h after training with a tone impairs context-specific freezing but does not impair freezing in response to the tone. Mice were trained and tested with a tone conditioned stimulus (CS), which produced lower levels of cue-evoked freezing when tested 24 h following training than did a noise cue (Fig. 1). (A) Mice sleep deprived from 0–5 h after training freeze less in response to the shocked context than do nonsleep-deprived mice, although this result did not reach statistical significance (context; P = 0.077; n = 12 per group). Sleep-deprived mice did not differ significantly from nonsleep-deprived mice in freezing in the altered chamber (pre CS) or in freezing in response to the cue (CS; P's > .05; n = 12 per group). (B) Mice show a deficit in the specificity of freezing to the shocked context when sleep deprived from 0–5 h after training with a tone. Specificity of freezing to the shocked context (delta context) measured by the difference in percent freezing between the shocked and altered context was significantly less in mice that were sleep deprived from 0–5 h after training than in nonsleep-deprived mice (P < .05; n = 12 per group). Cue-specific freezing (delta cue) is not significantly altered by sleep deprivation from 0–5 h after training (P > .05; n = 12 per group). *, P < .05.

Figure 4

Total sleep deprivation from 5–10 h after training does not impair contextual or cued fear conditioning. (A) Sleep-deprived mice (n = 20) were not significantly different in levels of freezing in response to the shocked context than nonsleep-deprived mice (n = 19 per group; P > .05). Sleep-deprived mice did not differ from nonsleep-deprived mice in freezing in the altered chamber (pre CS) or in freezing in response to the cue (n = 19 per group; P > .05). (B) Specificity of freezing to the shocked context (delta context) measured by the difference in percent freezing between the shocked and altered context was not different in mice that were sleep-deprived from 5–10 h after training than in nonsleep-deprived mice (n = 19 per group; P > .05). Cue-specific freezing (delta cue) is not altered by sleep deprivation from 5–10 h after training (n = 19 per group; P > .05).