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.

Highlights

  • Fear conditioning is among the most widely used associative learning and memory tests, especially in laboratory animals such as mice and rats [1,2,3]

  • Our finding here suggests that while heart rate (HR) itself is an important parameter, heart rate variability (HRV) dynamics can serve as a sensitive measurement for reflecting emotional states when recalling short-term and longterm contextual and cued fear memories

  • Because of the well-defined cues and memory produced by fear conditioning paradigms, extensive efforts have been invested in electrophysiological analyses of neural changes in the brain [5,24,25,26,27,28,29,30]

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Summary

Introduction

Fear conditioning is among the most widely used associative learning and memory tests, especially in laboratory animals such as mice and rats [1,2,3]. There are several variations in terms of the nature of conditioned (tone, light, odor, environment, etc.) and unconditioned stimuli (mild electrical footshock, air-puff to eyelid, etc.). These fear conditioning protocols can produce long-lasting associative memories in the brains of various animal species, ranging from flies to mice to humans. It has been shown that contextual fear conditioning is hippocampal dependent, whereas cued fear conditioning is hippocampal independent [1,2,7] Both types of fear conditioning require the activation of the NMDA receptors [8,9,10,11,12]

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