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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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Increased duration of heart rate variability stage-I in long-term contextual memory retention test.(A) The instant HR responses of an individual mouse showed clearly two distinct stages: stage-I (red) and stage-II (blue) during the contextual habituation and retention tests. Upper panel: contextual habituation; Middle panel: 1-hr contextual retention test; Lower panel: 1-day contextual retention test. The freezing responses were plotted on top of the instant HR; freezing state, red bar; non-freezing state, blue bar. The blue vertical line indicates the start of stage-I; the red vertical line indicates the end of stage-I; the green vertical line indicates the end of the contextual retention test. (B) Poincaré plots of the same mouse’s R-R intervals of 1-min duration in prior (grey line), stage-I (red line) and stage-II (blue line). The prior was a 3-min period before contextual habituation or retention. Upper panel: contextual habituation; Middle panel: 1-hr contextual retention test; Lower panel: 1-day contextual retention test. (C-D) The HR and CV of prior, stage-I and stage-II during 1-hr contextual retention. Error bars, s.e.m.; n = 11; *P<0.05, ***P<0.001, one-way repeated measures ANOVA and Tukey post hoc test.
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pone-0063590-g004: Increased duration of heart rate variability stage-I in long-term contextual memory retention test.(A) The instant HR responses of an individual mouse showed clearly two distinct stages: stage-I (red) and stage-II (blue) during the contextual habituation and retention tests. Upper panel: contextual habituation; Middle panel: 1-hr contextual retention test; Lower panel: 1-day contextual retention test. The freezing responses were plotted on top of the instant HR; freezing state, red bar; non-freezing state, blue bar. The blue vertical line indicates the start of stage-I; the red vertical line indicates the end of stage-I; the green vertical line indicates the end of the contextual retention test. (B) Poincaré plots of the same mouse’s R-R intervals of 1-min duration in prior (grey line), stage-I (red line) and stage-II (blue line). The prior was a 3-min period before contextual habituation or retention. Upper panel: contextual habituation; Middle panel: 1-hr contextual retention test; Lower panel: 1-day contextual retention test. (C-D) The HR and CV of prior, stage-I and stage-II during 1-hr contextual retention. Error bars, s.e.m.; n = 11; *P<0.05, ***P<0.001, one-way repeated measures ANOVA and Tukey post hoc test.

Mentions: To understand how HRV and HR change during memory retrieval, we conducted contextual fear retention tests, first with 1-hr retention test, and then followed by 1-day retention test. During the 1-hr contextual retention test (15-min), the instant HR showed a 2-stage profile (Figure 4A). The first stage was characterized as a 'plateau' (stage-I) during which HR was increased (HR  = 748 bpm) but HRV was extremely small (CV  = 0.49%), whereas the second stage was characterized as lifted instant HR but slightly increased CV of instant HR. The Poincaré plot of R-R intervals of habituation session showed the existence of two distinct HRV stages (Figure 4B, top row), but with a shorter stage-I duration and larger variability in stage-II. During contextual fear recall, the HR significantly increased when mice were introduced into the fearful context in 1-hr contextual retention or 1-day contextual retention test (Figure 4A). Moreover, HRV also showed greater reduction during 1-hr or 1-day contextual retention tests. We observed that consolidation of short-term contextual fear memory into long-term memory was associated with an increase in the HRV stage-I duration (Figure 4A) as well as more tightly regulated HRV in the stage-II (Figure 4B). Our quantitative analyses show that HR did not show significant difference between these two stages during contextual recall although both were significantly higher than the base rate (Figure 4C, P<0.001). However, HRV, as measured by the CV of instant HR, revealed the significant difference between the two stages as well as to that of the baseline prior to recall (Figure 4D, P<0.05, 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)

Increased duration of heart rate variability stage-I in long-term contextual memory retention test.(A) The instant HR responses of an individual mouse showed clearly two distinct stages: stage-I (red) and stage-II (blue) during the contextual habituation and retention tests. Upper panel: contextual habituation; Middle panel: 1-hr contextual retention test; Lower panel: 1-day contextual retention test. The freezing responses were plotted on top of the instant HR; freezing state, red bar; non-freezing state, blue bar. The blue vertical line indicates the start of stage-I; the red vertical line indicates the end of stage-I; the green vertical line indicates the end of the contextual retention test. (B) Poincaré plots of the same mouse’s R-R intervals of 1-min duration in prior (grey line), stage-I (red line) and stage-II (blue line). The prior was a 3-min period before contextual habituation or retention. Upper panel: contextual habituation; Middle panel: 1-hr contextual retention test; Lower panel: 1-day contextual retention test. (C-D) The HR and CV of prior, stage-I and stage-II during 1-hr contextual retention. Error bars, s.e.m.; n = 11; *P<0.05, ***P<0.001, one-way repeated measures ANOVA and Tukey post hoc test.
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pone-0063590-g004: Increased duration of heart rate variability stage-I in long-term contextual memory retention test.(A) The instant HR responses of an individual mouse showed clearly two distinct stages: stage-I (red) and stage-II (blue) during the contextual habituation and retention tests. Upper panel: contextual habituation; Middle panel: 1-hr contextual retention test; Lower panel: 1-day contextual retention test. The freezing responses were plotted on top of the instant HR; freezing state, red bar; non-freezing state, blue bar. The blue vertical line indicates the start of stage-I; the red vertical line indicates the end of stage-I; the green vertical line indicates the end of the contextual retention test. (B) Poincaré plots of the same mouse’s R-R intervals of 1-min duration in prior (grey line), stage-I (red line) and stage-II (blue line). The prior was a 3-min period before contextual habituation or retention. Upper panel: contextual habituation; Middle panel: 1-hr contextual retention test; Lower panel: 1-day contextual retention test. (C-D) The HR and CV of prior, stage-I and stage-II during 1-hr contextual retention. Error bars, s.e.m.; n = 11; *P<0.05, ***P<0.001, one-way repeated measures ANOVA and Tukey post hoc test.
Mentions: To understand how HRV and HR change during memory retrieval, we conducted contextual fear retention tests, first with 1-hr retention test, and then followed by 1-day retention test. During the 1-hr contextual retention test (15-min), the instant HR showed a 2-stage profile (Figure 4A). The first stage was characterized as a 'plateau' (stage-I) during which HR was increased (HR  = 748 bpm) but HRV was extremely small (CV  = 0.49%), whereas the second stage was characterized as lifted instant HR but slightly increased CV of instant HR. The Poincaré plot of R-R intervals of habituation session showed the existence of two distinct HRV stages (Figure 4B, top row), but with a shorter stage-I duration and larger variability in stage-II. During contextual fear recall, the HR significantly increased when mice were introduced into the fearful context in 1-hr contextual retention or 1-day contextual retention test (Figure 4A). Moreover, HRV also showed greater reduction during 1-hr or 1-day contextual retention tests. We observed that consolidation of short-term contextual fear memory into long-term memory was associated with an increase in the HRV stage-I duration (Figure 4A) as well as more tightly regulated HRV in the stage-II (Figure 4B). Our quantitative analyses show that HR did not show significant difference between these two stages during contextual recall although both were significantly higher than the base rate (Figure 4C, P<0.001). However, HRV, as measured by the CV of instant HR, revealed the significant difference between the two stages as well as to that of the baseline prior to recall (Figure 4D, P<0.05, 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