Published on Wed Jun 30 2021

Parametric modulators of sex-biased conditioned fear responding

Mitchell, J. R., Trettel, S. G., Li, A. J., Wasielewski, S., Huckleberry, K. A., Fanikos, M., Golden, E., Shansky, R. M.

Pavlovian fear conditioning is a widely used behavioral paradigm for studying associative learning in rodents. We previously reported that female Sprague Dawley rats are more likely than males to engage in darting. We find that like freezing, darting probability scales with experimental alterations in multiple dimensions.

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Abstract

Pavlovian fear conditioning is a widely used behavioral paradigm for studying associative learning in rodents. Despite early recognition that subjects may engage in a variety of behaviors that reflect the experimental parameters of a given protocol, the last several decades have seen the field narrow its focus to measure freezing as the sole indicator of conditioned fear. Additionally, unconditioned responses such as shock-related activity are rarely considered. We previously reported that female Sprague Dawley rats are more likely than males to engage in darting, an escape-like conditioned response that is associated with heightened shock reactivity, but we did not establish whether darting was sensitive to manipulations of factors such as chamber size, shock intensity, or number of trials. Our goal here was to address these questions by defining parametric and phenotypic predictors of darting in both sexes. To better capture fear-related behavioral repertoires in our animals, we developed ScaredyRat, a custom Python tool that analyzes Noldus Ethovision-generated raw data files to identify Darters and quantify both conditioned and unconditioned responses. We find that like freezing, darting probability scales with experimental alterations in multiple dimensions. In most cases, the sex bias towards females persists, but males will transition to darting in extended, or overtraining fear conditioning protocols.