Effects of stressor predictability on escape learning and sleep in mice

Abstract

Study objectives: Controllable stress, modeled by escapable shock (ES), can produce significant alterations in post-stress sleep, including increased rapid eye movement (REM) sleep. Recent work has demonstrated that post-stress sleep may be influenced by stressor predictability, modeled by predictive auditory cues. In this study, we trained mice with ES, either signaled (SES) or unsignaled (UES) by auditory cues, and investigated the effects of predictability on escape learning and sleep associated with ES.

Design: Adult male BALB/cJ mice were implanted for recording electroencephalography and activity via telemetry. After the mice recovered from surgery, baseline sleep recordings were obtained. The mice were then randomly assigned to SES and UES conditions. Both groups had control over the duration of footshocks (0.5 mA; 5.0 sec maximum duration) by moving to the non-occupied chamber in a shuttlebox. SES mice were presented tones (90 dB, 2 kHz, 10 sec maximum duration) that started 5.0 sec prior to and co-terminated with footshocks. UES mice were presented identical tones that were not synchronized to shock presentation. ES training continued for 2 consecutive days (EST1 and EST2) with 20 footshock presentations (1 min inter-stimulus intervals). Seven days after EST2, the animals were re-exposed to the training chamber (context) alone for 30 min.

Measurements and results: Escape latency was used to determine successful or unsuccessful escape learning. Sleep was scored for 20 h for baseline and on each treatment day. Freezing in the training context was scored as a behavioral index of fear. Nine of 14 SES mice successfully learned escape (SESl), and 5 failed to learn escape (SESf). Compared with baseline, SESl mice, but not SESf mice, showed significantly increased post-shock REM. All UES mice learned escape and showed enhanced post-shock REM. Freezing and sleep did not differ among groups on the context re-exposure day.

Conclusions: The results indicate that information available in a stressful situation can affect an animal's ability to learn an appropriate response and post-stress sleep.

Citation: Machida M; Yang L; Wellman LL; Sanford LD. Effects of stressor predictability on escape learning and sleep in mice. SLEEP 2013;36(3):421-430.

Keywords: Controllability; escape learning; mice; predictability; rapid eye movement (REM) sleep; sleep; stress.

Figure 1

Shock escape latency and total shock durations received by mice trained with signaled escapable shock (SES, n = 14) and unsignaled escapable shock (UES, n = 10) across two training days (EST1, EST2). (A) Average shock escape latency for UES mice across 20 individual shock trials during EST1 and EST2 (*P < 0.05 between EST1 and EST2). (B) Average shock escape latency for all SES mice across 20 individual shock trials during EST1 and EST2. (C) Average shock escape latency for SES failed (SESf), SES learned (SESl), and UES mice during EST1 presented in four-trial blocks (*P < 0.05 between SESf and SESl). (D) Average shock escape latency for SESl, SESf, and UES mice during EST2 presented in four-trial blocks (*P < 0.05 between SESf and SESl). (E) Total shock duration presented to UES, SES collectively and separately as SESf and SESl during EST1 and EST2 (*P < 0.05 between EST1 and EST2). Error bars are ± SEM.

Figure 2

Behavioral freezing exhibited during re-exposure to the shock context alone. (A) Percent time freezing plotted for the 5-min pre-shock period (PS) and for the entire 30-min context re-exposure after the mice had two shock training sessions. (B) Percent time freezing plotted for PS and in 5-min blocks across context re-exposure. Freezing did not significantly differ among groups.

Figure 3

Selected sleep and waking parameters plotted as 20-h totals for Baseline, EST1, EST2, and the context test day (Context). (A) Total non-rapid eye movement (NREM). (B) Total sleep time (TST). (C) Active wakefulness (AW). (D) Quiet wakefulness (QW). SESf, failed escape; SESl, learned escape; UES, unsignaled escapable shock. *P < 0.05 for SESl compared with baseline; ⁺P < 0.05, UES compared with baseline; ^&P < 0.05, SESf compared with baseline. Error bars are ± SEM.

Figure 4

Selected REM parameters plotted at 20-hr totals for Baseline, EST1, EST2, and Context. (A) Total time spent for REM. (B) Number of REM episodes. Error bars are ± SEM. SESf, failed escape; SESl, learned escape; UES, unsignaled escapable shock. *P < 0.05 for SESl compared with baseline; ⁺P < 0.05, UES compared to baseline. ^#P < 0.05 for comparisons between SESl and SESf.

Figure 5

REM percentage plotted for the first 4 h (the fifth to eighth h after lights on) of Baseline and Context in (A) SESl, (B) SESf, and (C) UES mice. Error bars are ± SEM. *P < 0.05 compared with baseline. SESf, failed escape; SESl, learned escape; UES, unsignaled escapable shock.