Differential behavioral, stress, and sleep responses in mice with different delays of fear extinction

Sleep. 2019 Oct 9;42(10):zsz147. doi: 10.1093/sleep/zsz147.


Study objectives: Sleep, in particular rapid eye movement (REM), has been linked to fear learning and extinction; however, their relationship is poorly understood. We determined how different delays of extinction training (ET) impact fear-conditioned behaviors, changes in sleep, and stress responses.

Methods: EEG activity, movement, and body temperature in mice were monitored via telemetry. Following contextual fear conditioning (shock training [ST]), separate groups of mice were reexposed to the context at 24-hour post-ST (24h ET-1) and at 48-hour post-ST (48h ET-1). Post-ET sleep amount and sleep-associated EEG (delta and theta) activity were compared to baseline and to post-ST sleep. Freezing, locomotion, grooming, and rearing were monitored to determine effects of ET on fear behaviors. Body temperature immediately after ET was monitored to assess stress-induced hyperthermia (SIH).

Results: 24h ET-1 and 48h ET-1 produced similar freezing and REM reductions, but dissimilar rearing activity and SIH. 24h ET-1 was followed by periods of suppressed REM-associated theta (REM-θ) activity, immediately after ET and during the subsequent dark period. Suppressed REM-θ was specific to sleep after 24h ET-1, and did not occur after ST, nor after 48h ET-1.

Conclusions: ET-1 at 24 and 48 hours after ST was associated with similar freezing and REM amounts, but with differences in other overt behaviors, in REM-θ, and in SIH. Freezing was not predictive of changes in other fear-associated responses. This study demonstrated that consideration of time delay from fear acquisition to extinction is important when assessing the relationships between extinction and behavior, sleep, and stress responses.

Keywords: REM; REM-θ activity; contextual fear conditioning; fear extinction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Electroencephalography / methods
  • Extinction, Psychological / physiology*
  • Fear / physiology*
  • Fear / psychology
  • Freezing Reaction, Cataleptic / physiology*
  • Locomotion / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Sleep / physiology*
  • Sleep, REM / physiology
  • Stress, Psychological / physiopathology*
  • Stress, Psychological / psychology
  • Time Factors