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Changes in heart rate variability are associated with expression of short-term and long-term contextual and cued fear memories.

Liu J, Wei W, Kuang H, Zhao F, Tsien JZ - PLoS ONE (2013)

Bottom Line: We found that while fear conditioning could increase heart rate, the most significant change was the reduction in heart rate variability which could be further divided into two distinct stages: a highly rhythmic phase (stage-I) and a more variable phase (stage-II).We showed that the time duration of the stage-I rhythmic phase were sensitive enough to reflect the transition from short-term to long-term fear memories.Moreover, it could also detect fear extinction effect during the repeated tone recall.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Brain Functional Genomics (Ministry of Education), Institute of Brain Functional Genomics, East China Normal University, Shanghai, China.

ABSTRACT
Heart physiology is a highly useful indicator for measuring not only physical states, but also emotional changes in animals. Yet changes of heart rate variability during fear conditioning have not been systematically studied in mice. Here, we investigated changes in heart rate and heart rate variability in both short-term and long-term contextual and cued fear conditioning. We found that while fear conditioning could increase heart rate, the most significant change was the reduction in heart rate variability which could be further divided into two distinct stages: a highly rhythmic phase (stage-I) and a more variable phase (stage-II). We showed that the time duration of the stage-I rhythmic phase were sensitive enough to reflect the transition from short-term to long-term fear memories. Moreover, it could also detect fear extinction effect during the repeated tone recall. These results suggest that heart rate variability is a valuable physiological indicator for sensitively measuring the consolidation and expression of fear memories in mice.

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Changes of heart rate and heart rate variability during 1-day cued fear retention tests.(A) Instant HR responses of the same mouse during three recall trials, trial#1, trial#5 and trial#7. The freezing responses were plotted on top of the instant HR; freezing state, red bar; non-freezing state, blue bar. The blue vertical lines indicate the onset and offset of the tone (30 seconds). (B) Poincaré plots of the same mouse’s R-R intervals of 30-sec pre-tone (grey line) and 30-sec during-tone (blue line and red line) in trial #1, trial #5 and trial #7. The blue line indicates the rising phase of instant HR, which was defined as a period from the onset of tone to the time when HRV reached the stage-I plateau. (C–E) The freezing responses, HR and CV of pre-tone, during-tone and post-tone during 1-day auditory cued retention. n = 8; *P<0.05, **P<0.01, ***P<0.001, paired t test. (F) The stage-I plateau durations during 1-day auditory cued retention. n = 8; **P<0.01, ***P<0.001, one-way repeated measures ANOVA and Dunnett’s multiple comparisons test. Dunnett’s multiple comparisons test comparing with recall trial #1 showed that extinction effect reached significant difference at trial #5. (G–H) The HR and CV of the during-tone and post-tone freezing period in 1-day auditory cued retention test. n = 8; ***P<0.001, paired t test. All data are plotted as mean ± s.e.m. (error bars).
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pone-0063590-g007: Changes of heart rate and heart rate variability during 1-day cued fear retention tests.(A) Instant HR responses of the same mouse during three recall trials, trial#1, trial#5 and trial#7. The freezing responses were plotted on top of the instant HR; freezing state, red bar; non-freezing state, blue bar. The blue vertical lines indicate the onset and offset of the tone (30 seconds). (B) Poincaré plots of the same mouse’s R-R intervals of 30-sec pre-tone (grey line) and 30-sec during-tone (blue line and red line) in trial #1, trial #5 and trial #7. The blue line indicates the rising phase of instant HR, which was defined as a period from the onset of tone to the time when HRV reached the stage-I plateau. (C–E) The freezing responses, HR and CV of pre-tone, during-tone and post-tone during 1-day auditory cued retention. n = 8; *P<0.05, **P<0.01, ***P<0.001, paired t test. (F) The stage-I plateau durations during 1-day auditory cued retention. n = 8; **P<0.01, ***P<0.001, one-way repeated measures ANOVA and Dunnett’s multiple comparisons test. Dunnett’s multiple comparisons test comparing with recall trial #1 showed that extinction effect reached significant difference at trial #5. (G–H) The HR and CV of the during-tone and post-tone freezing period in 1-day auditory cued retention test. n = 8; ***P<0.001, paired t test. All data are plotted as mean ± s.e.m. (error bars).

Mentions: Next, we asked how expression of long-term fear memory affected HR and HRV by conducting 1-day cued retention test. Similar to short-term cued recall, tone induced changes in HRV and HR (Figure 7A). The Poincaré plot showed more stable conditioned responses during tone recall (Figure 7B). Freezing behavior during the 30-sec tone period was significantly higher than that of post-tone period in most trials and became much more consistent (Figure 7C, P<0.05). The during-tone HR was significantly higher than post-tone HR, (Figure 7D, P<0.01, P<0.001). Also, the during-tone HRV was significantly lower than post-tone HRV (Figure 7E, P<0.01, P<0.001). Although the heartbeat regularity during tone was much more stable throughout trials in comparison to short-term retention test, statistical analysis shows that the extinction effect, as indicated by reduction in the stage-I plateau duration, was clearly noticeable (Figure 7F, P<0.01, P<0.001). Consistent with those observed in 1-hr cued retention tests, the HR of during-tone freezing period was also significantly higher than that of post-tone freezing state (Figure 7G, P<0.001). Moreover, the during-tone HRV was significantly lower than the post-tone HRV in freezing (Figure 7H, P<0.001).


Changes in heart rate variability are associated with expression of short-term and long-term contextual and cued fear memories.

Liu J, Wei W, Kuang H, Zhao F, Tsien JZ - PLoS ONE (2013)

Changes of heart rate and heart rate variability during 1-day cued fear retention tests.(A) Instant HR responses of the same mouse during three recall trials, trial#1, trial#5 and trial#7. The freezing responses were plotted on top of the instant HR; freezing state, red bar; non-freezing state, blue bar. The blue vertical lines indicate the onset and offset of the tone (30 seconds). (B) Poincaré plots of the same mouse’s R-R intervals of 30-sec pre-tone (grey line) and 30-sec during-tone (blue line and red line) in trial #1, trial #5 and trial #7. The blue line indicates the rising phase of instant HR, which was defined as a period from the onset of tone to the time when HRV reached the stage-I plateau. (C–E) The freezing responses, HR and CV of pre-tone, during-tone and post-tone during 1-day auditory cued retention. n = 8; *P<0.05, **P<0.01, ***P<0.001, paired t test. (F) The stage-I plateau durations during 1-day auditory cued retention. n = 8; **P<0.01, ***P<0.001, one-way repeated measures ANOVA and Dunnett’s multiple comparisons test. Dunnett’s multiple comparisons test comparing with recall trial #1 showed that extinction effect reached significant difference at trial #5. (G–H) The HR and CV of the during-tone and post-tone freezing period in 1-day auditory cued retention test. n = 8; ***P<0.001, paired t test. All data are plotted as mean ± s.e.m. (error bars).
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pone-0063590-g007: Changes of heart rate and heart rate variability during 1-day cued fear retention tests.(A) Instant HR responses of the same mouse during three recall trials, trial#1, trial#5 and trial#7. The freezing responses were plotted on top of the instant HR; freezing state, red bar; non-freezing state, blue bar. The blue vertical lines indicate the onset and offset of the tone (30 seconds). (B) Poincaré plots of the same mouse’s R-R intervals of 30-sec pre-tone (grey line) and 30-sec during-tone (blue line and red line) in trial #1, trial #5 and trial #7. The blue line indicates the rising phase of instant HR, which was defined as a period from the onset of tone to the time when HRV reached the stage-I plateau. (C–E) The freezing responses, HR and CV of pre-tone, during-tone and post-tone during 1-day auditory cued retention. n = 8; *P<0.05, **P<0.01, ***P<0.001, paired t test. (F) The stage-I plateau durations during 1-day auditory cued retention. n = 8; **P<0.01, ***P<0.001, one-way repeated measures ANOVA and Dunnett’s multiple comparisons test. Dunnett’s multiple comparisons test comparing with recall trial #1 showed that extinction effect reached significant difference at trial #5. (G–H) The HR and CV of the during-tone and post-tone freezing period in 1-day auditory cued retention test. n = 8; ***P<0.001, paired t test. All data are plotted as mean ± s.e.m. (error bars).
Mentions: Next, we asked how expression of long-term fear memory affected HR and HRV by conducting 1-day cued retention test. Similar to short-term cued recall, tone induced changes in HRV and HR (Figure 7A). The Poincaré plot showed more stable conditioned responses during tone recall (Figure 7B). Freezing behavior during the 30-sec tone period was significantly higher than that of post-tone period in most trials and became much more consistent (Figure 7C, P<0.05). The during-tone HR was significantly higher than post-tone HR, (Figure 7D, P<0.01, P<0.001). Also, the during-tone HRV was significantly lower than post-tone HRV (Figure 7E, P<0.01, P<0.001). Although the heartbeat regularity during tone was much more stable throughout trials in comparison to short-term retention test, statistical analysis shows that the extinction effect, as indicated by reduction in the stage-I plateau duration, was clearly noticeable (Figure 7F, P<0.01, P<0.001). Consistent with those observed in 1-hr cued retention tests, the HR of during-tone freezing period was also significantly higher than that of post-tone freezing state (Figure 7G, P<0.001). Moreover, the during-tone HRV was significantly lower than the post-tone HRV in freezing (Figure 7H, P<0.001).

Bottom Line: We found that while fear conditioning could increase heart rate, the most significant change was the reduction in heart rate variability which could be further divided into two distinct stages: a highly rhythmic phase (stage-I) and a more variable phase (stage-II).We showed that the time duration of the stage-I rhythmic phase were sensitive enough to reflect the transition from short-term to long-term fear memories.Moreover, it could also detect fear extinction effect during the repeated tone recall.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Brain Functional Genomics (Ministry of Education), Institute of Brain Functional Genomics, East China Normal University, Shanghai, China.

ABSTRACT
Heart physiology is a highly useful indicator for measuring not only physical states, but also emotional changes in animals. Yet changes of heart rate variability during fear conditioning have not been systematically studied in mice. Here, we investigated changes in heart rate and heart rate variability in both short-term and long-term contextual and cued fear conditioning. We found that while fear conditioning could increase heart rate, the most significant change was the reduction in heart rate variability which could be further divided into two distinct stages: a highly rhythmic phase (stage-I) and a more variable phase (stage-II). We showed that the time duration of the stage-I rhythmic phase were sensitive enough to reflect the transition from short-term to long-term fear memories. Moreover, it could also detect fear extinction effect during the repeated tone recall. These results suggest that heart rate variability is a valuable physiological indicator for sensitively measuring the consolidation and expression of fear memories in mice.

Show MeSH