Abstract
Post-learning sleep facilitates negative memory consolidation and also helps preserve it over several years. It is believed, therefore, that sleep deprivation may help prevent consolidation of fearful memory. Its effect, however, on consolidation of negative/frightening memories is not known. Cued fear-conditioning (CuFC) is a widely used model to understand the neural basis of negative memory associated with anxiety disorders. In this study, we first determined the suitable circadian timing for consolidation of CuFC memory and changes in sleep architecture after CuFC. Thereafter, we studied the effect of sleep deprivation on CuFC memory consolidation. Three sets of experiments were performed in male Wistar rat (n = 51). In experiment-I, animals were conditioned to cued-fear by presenting ten tone-shock paired stimuli during lights-on (7 AM) (n = 9) and lights-off (7 PM) (n = 9) periods. In experiment-II, animals were prepared for polysomnographic recording (n = 8) and changes in sleep architecture after CuFC was determined. Further in experiment-III, animals were cued fear-conditioned during the lights-off period and were randomly divided into four groups: Sleep-Deprived (SD) (n = 9), Non-Sleep Deprived (NSD) (n = 9), Stress Control (SC) (n = 9) and Tone Control (n = 7). Percent freezing amount, a hallmark of fear, was compared statistically in these groups. Rats trained during the lights-off period exhibited significantly more freezing compared to lights-on period. In CuFC trained animals, total sleep amount did not change, however, REM sleep decreased significantly. Further, out of total sleep time, animals spent proportionately more time in NREM sleep. Nevertheless, SD animals exhibited significantly less freezing compared to NSD and SC groups. These data suggest that sleep plays an important role in the consolidation of cued fear-conditioned memory.
Highlights
Learning about fear could be an advantageous response mechanism but if its expression becomes too generalized, it leads to disorders associated with negative emotional memory
Rats trained for cued fear-conditioning both during lights-on (n = 9) and lights-off (n = 9) phases showed significant conditioning effect of tone during testing compared to baseline day (Figure 2A and B)
These results suggest that rats trained for cued fear-conditioning during the lights-off phase showed a significantly better learning compared to rats trained during the lights-on phase
Summary
Learning about fear could be an advantageous response mechanism but if its expression becomes too generalized, it leads to disorders associated with negative emotional memory. In cued fear-conditioning (CuFC), neutral conditioned stimulus (CS) (for example, light or tone) is paired with the fear inducing unconditioned stimulus (US) (such as foot-shock). Since both the stimuli are presented in a paired fashion during training, an emotionally neutral stimulus (tone/light) acquires fear inducing properties. Animals trained for fear conditioning exhibit synaptic plasticity in the amygdala [7] and subjects with anxiety disorders exhibit hyperactive amygdalar response to fearful stimuli [8]. Understanding about the impairment in consolidation of fearful memory may provide preventive clinical benefits in developing disorders associated with emotional memory
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