Q&A Report: Quantifying Cardiovascular and Behavioral Correlates of Fear in Mice: Implications for PTSD and Cardiovascular Disease Risk

How much does the cardiovascular response vary depending on the behavioral paradigm (i.e. fear conditioning vs. anxiety tasks)?

The cardiovascular response using wireless telemetry to conditioned threats vs generalized anxiety tests certainly can vary.  This is influenced by environmental context (novel vs home cage), level of habituation to testing environment and intensity level of unconditioned stimuli (US).

For further examples please refer to the following papers:

Turley, B., Swiercz, A.P., Iyer, L., Marvar, P.J. Internal state-dependent conditioned stimulus delivery using cardiovascular telemetry in mice.  Physiology and Behavior 2021

Swiercz AP, Seligowski AV, Park J, Marvar PJ. Extinction of Fear Memory Attenuates Conditioned   Cardiovascular Fear Reactivity. Front Behav Neurosci. 2018 Nov 13;12:276

What are your thoughts on combining fear conditioning with cardiovascular challenge (MI/TAC) and endpoint evaluations such (e.g. PV Loops) instead of telemetry?

This is an excellent suggestion as it would allow for one to further examine causal roles and mechanism(s) of cardiovascular disease risk factors (ie., myocardial infarction) and impact on fear learning and memory.  Such as study would likely elucidate further potential mechanisms that link PTSD to CVD and vice versa.

Did you assess the stress hormone profile during extinction training? Could stress hormnes have a role in the cardiovascular responses?

In previous studies we and other labs have accessed stress hormones (ie., cortisol levels) in the context of fear learning and extinction paradigms and indeed they play an important role in both memory and the cardiovascular response (ie., fight or flight).  In these particular studies we did not profile stress hormone levels across the time course of the study used here but would predict low circulating corticosterone levels following extinction of learned fear, compared to animals that did not undergo extinction learning.

Does the mouse’s exposure to foot shock disrupt the DSI telemetry device?

No, the foot shock does not disrupt the telemetry device or the recording of data during fear conditioning.

In the "Internal state-dependent" paper, what was the rationale for reporting time-domain HR measures and not frequency or entropic measures?

In this paper (Turley et al., 2021), the study goal was to implement a telemetry software that allows for delivery of a conditioned stimulus (CS) (ie., audible tone) when the blood pressure is in a set-range, while simultaneously assessing both the conditioned blood pressure and heart rate parameters to the CS.   Including additional frequency analysis / entropic measures for further assessing autonomic arousal to the CS in different environmental states is a great suggestion, however for this particular paper we did not include this analysis.  This was partly based on the goals of the study, but certainly a future consideration that would be important to include for analysis when further probing underlying mechanisms for autonomic dysfunction in PTSD.