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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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Effects of fear conditioning on heart rate and heart rate variability.(A) Illustration of a fear conditioning chamber for producing a tone-shock pairing fear memory. (B) A 30-sec neural tone (85 dB, 5000 Hz) co-terminates with a 2-sec mild foot shock (0.75 mA). (C) Schematic representation of experimental paradigm for cued fear conditioning. (D) Instant HR responses of an individual mouse during three CS-US pairings, trial#1, trial#4 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); the red vertical line indicates the onset of the foot shock (2 seconds). (E) Poincaré plots of the same mouse’s R-R intervals of 28-sec tone duration in trial#1, trial#4 and trial#7. (F) The average HR of 28-sec tone duration during training. (G) The average CV of instant HR of 28-sec tone duration during training. (F) The average freezing responses of 28-sec tone duration during training. Error bars, s.e.m.; n = 11; ***P<0.001, one-way repeated measures ANOVA and Tukey post hoc test.
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pone-0063590-g003: Effects of fear conditioning on heart rate and heart rate variability.(A) Illustration of a fear conditioning chamber for producing a tone-shock pairing fear memory. (B) A 30-sec neural tone (85 dB, 5000 Hz) co-terminates with a 2-sec mild foot shock (0.75 mA). (C) Schematic representation of experimental paradigm for cued fear conditioning. (D) Instant HR responses of an individual mouse during three CS-US pairings, trial#1, trial#4 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); the red vertical line indicates the onset of the foot shock (2 seconds). (E) Poincaré plots of the same mouse’s R-R intervals of 28-sec tone duration in trial#1, trial#4 and trial#7. (F) The average HR of 28-sec tone duration during training. (G) The average CV of instant HR of 28-sec tone duration during training. (F) The average freezing responses of 28-sec tone duration during training. Error bars, s.e.m.; n = 11; ***P<0.001, one-way repeated measures ANOVA and Tukey post hoc test.

Mentions: To produce fear conditioning memories, we used classic conditioned stimulus (CS, 30-sec tone, 85 dB, 5000 Hz) which was co-terminated with a brief 2-sec unconditioned stimulus (US, foot shock, 0.75 mA) during the acquisition phase (Fig. 3A and 3B). To provide a detailed understanding of how fearful emotion may evolve during the learning phase, we used a seven CS/US-pairing protocol with 3–5 min randomized interval between each CS-US pairing. For measuring HR dynamics during recall, we performed contextual and cued retention tests at 1-hr (short-term memory) and 1-day (long-term memory) (Fig. 3C). To prevent potential fear extinction during short-term retention, the mice were subjected to one more CS/US pairing before being brought back to home cages for rest. The long-term fear memory was measured at 1-day intervals for both contextual and cued retention tests (24 hours later) (Fig. 3C).


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)

Effects of fear conditioning on heart rate and heart rate variability.(A) Illustration of a fear conditioning chamber for producing a tone-shock pairing fear memory. (B) A 30-sec neural tone (85 dB, 5000 Hz) co-terminates with a 2-sec mild foot shock (0.75 mA). (C) Schematic representation of experimental paradigm for cued fear conditioning. (D) Instant HR responses of an individual mouse during three CS-US pairings, trial#1, trial#4 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); the red vertical line indicates the onset of the foot shock (2 seconds). (E) Poincaré plots of the same mouse’s R-R intervals of 28-sec tone duration in trial#1, trial#4 and trial#7. (F) The average HR of 28-sec tone duration during training. (G) The average CV of instant HR of 28-sec tone duration during training. (F) The average freezing responses of 28-sec tone duration during training. Error bars, s.e.m.; n = 11; ***P<0.001, one-way repeated measures ANOVA and Tukey post hoc test.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3646801&req=5

pone-0063590-g003: Effects of fear conditioning on heart rate and heart rate variability.(A) Illustration of a fear conditioning chamber for producing a tone-shock pairing fear memory. (B) A 30-sec neural tone (85 dB, 5000 Hz) co-terminates with a 2-sec mild foot shock (0.75 mA). (C) Schematic representation of experimental paradigm for cued fear conditioning. (D) Instant HR responses of an individual mouse during three CS-US pairings, trial#1, trial#4 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); the red vertical line indicates the onset of the foot shock (2 seconds). (E) Poincaré plots of the same mouse’s R-R intervals of 28-sec tone duration in trial#1, trial#4 and trial#7. (F) The average HR of 28-sec tone duration during training. (G) The average CV of instant HR of 28-sec tone duration during training. (F) The average freezing responses of 28-sec tone duration during training. Error bars, s.e.m.; n = 11; ***P<0.001, one-way repeated measures ANOVA and Tukey post hoc test.
Mentions: To produce fear conditioning memories, we used classic conditioned stimulus (CS, 30-sec tone, 85 dB, 5000 Hz) which was co-terminated with a brief 2-sec unconditioned stimulus (US, foot shock, 0.75 mA) during the acquisition phase (Fig. 3A and 3B). To provide a detailed understanding of how fearful emotion may evolve during the learning phase, we used a seven CS/US-pairing protocol with 3–5 min randomized interval between each CS-US pairing. For measuring HR dynamics during recall, we performed contextual and cued retention tests at 1-hr (short-term memory) and 1-day (long-term memory) (Fig. 3C). To prevent potential fear extinction during short-term retention, the mice were subjected to one more CS/US pairing before being brought back to home cages for rest. The long-term fear memory was measured at 1-day intervals for both contextual and cued retention tests (24 hours later) (Fig. 3C).

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
Related in: MedlinePlus