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Genetic variability in fear learning and awakenings to re-exposure of a novel conditioning stimulus during sleep

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Abstract

The impact of trauma exposure on sleep may depend on the interaction between biological vulnerability of the individual and environmental factors. We recently established a mouse model of posttraumatic stress disorder (PTSD) utilizing a novel conditioning stimulus (CS) with which to re-expose mice during sleep. The current study assessed the effect of re-exposure to the CS during sleep in genetically ‘anxious’ male mice (n = 11) relative to ‘non-anxious’ mice (n = 12). Mice were instrumented with EEG, EMG and EKG electrodes and given seven days of adaptation prior to a 24-h baseline sleep recording. Mice were fear conditioned over three series with five cycles of paired 3 % carbon dioxide (CO2; CS) predicting 0.5 mA footshocks. Mice were then re-exposed to either the CS or to air (control) during sleep and the impact on the sleep–wake cycle was assessed. Anxious mice had increased spontaneous awakenings during baseline sleep study and exhibited a robust learned bradycardic response (−90 ± 11 bpm) that habituated across series, whereas non-anxious mice exhibited a mild-to-moderate initial learned bradycardic response (−44 ± 16 bpm) that sensitized across series. Subsequent re-exposure to the CS during sleep produced a 50 % increase (P < 0.05) in awakenings from NREM sleep in anxious mice, whereas awakenings in non-anxious mice were unaffected. Thus, genetic background impacts the magnitude and pattern of fear-learning responses, and re-exposure to a learned CS during sleep in an ‘anxious’ phenotype lowers the threshold to increased awakenings from NREM sleep.

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Acknowledgments

The authors would like to acknowledge the funding for this study DM102174 and to acknowledge the technical training and assistance of Lia Romano.

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Correspondence to Angela L. McDowell.

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McDowell, A.L., McKeon, A.B., Germain, A. et al. Genetic variability in fear learning and awakenings to re-exposure of a novel conditioning stimulus during sleep. Sleep Biol. Rhythms 14, 165–175 (2016). https://doi.org/10.1007/s41105-015-0036-4

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  • DOI: https://doi.org/10.1007/s41105-015-0036-4

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