Heart rate and heart rate variability assessment identifies individual differences in fear response magnitudes to earthquake, free fall, and air puff in mice

Fear behaviors and fear memories in rodents have been traditionally assessed by the amount of freezing upon the presentation of conditioned cues or unconditioned stimuli. However, many experiences, such as encountering earthquakes or accidental fall from tree branches, may produce long-lasting fear memories but are behaviorally difficult to measure using freezing parameters. Here, we have examined changes in heartbeat interval dynamics as physiological readout for assessing fearful reactions as mice were subjected to sudden air puff, free-fall drop inside a small elevator, and a laboratory-version earthquake. We showed that these fearful events rapidly increased heart rate (HR) with simultaneous reduction of heart rate variability (HRV). Cardiac changes can be further analyzed in details by measuring three distinct phases: namely, the rapid rising phase in HR, the maximum plateau phase during which HRV is greatly decreased, and the recovery phase during which HR gradually recovers to baseline values. We showed that durations of the maximum plateau phase and HR recovery speed were quite sensitive to habituation over repeated trials. Moreover, we have developed the fear resistance index based on specific cardiac response features. We demonstrated that the fear resistance index remained largely consistent across distinct fearful events in a given animal, thereby enabling us to compare and rank individual mouse's fear responsiveness among the group. Therefore, the fear resistance index described here can represent a useful parameter for measuring personality traits or individual differences in stress-susceptibility in both wild-type mice and post-traumatic stress disorder (PTSD) models.