Behavioral and brain mechanisms mediating conditioned flight behavior in rats

Abstract

Environmental contexts can inform animals of potential threats, though it is currently unknown how context biases the selection of defensive behavior. Here we investigated context-dependent flight responses with a Pavlovian serial-compound stimulus (SCS) paradigm that evokes freeze-to-flight transitions. Similar to previous work in mice, we show that male and female rats display context-dependent flight-like behavior in the SCS paradigm. Flight behavior was dependent on contextual fear insofar as it was only evoked in a shock-associated context and was reduced in the conditioning context after context extinction. Flight behavior was only expressed to white noise regardless of temporal order within the compound. Nonetheless, rats that received unpaired SCS trials did not show flight-like behavior to the SCS, indicating it is associative. Finally, we show that pharmacological inactivation of two brain regions critical to the expression of contextual fear, the central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST), attenuates both contextual fear and flight responses. All of these effects were similar in male and female rats. This work demonstrates that contextual fear can summate with cued and innate fear to drive a high fear state and transition from post-encounter to circa-strike defensive modes.

Conditional Freezing, Flight and Darting?

“…While our 75 dB noise stimulus is less intense than the 98-120 dB noise used in typical acoustic startle studies, we are observing an unconditional noise elicited response that also decreases with habituation (Experiment 4). Furthermore, our data and those of Totty et al (2021) indicate that these responses require a fearful context in order to occur. Fear is well known to potentiate startle responses (Brown, et al, 1951;Davis, 1989).…”

“…Thus, the difference between the paired and unpaired groups reported by Totty et al (2021) Initial reports suggest a sex difference in this noise-elicited flight behavior such that female rats show more of this behavior than males (Gruene et al, 2015). Within each experiment, we found no such sex differences between male and female mice for the PAR and darting measures of flight behavior, and Totty et al (2021) similarly found no sex differences in such behavior in male and female rats. To further increase the power of such an analysis for sex differences, we pooled all of the groups across the four experiments which received noise-shock pairings.…”

“…Additionally, pairing a habituated stimulus with a US can also cause a return of the habituated alpha response and this loss of habituation is not observed when the two stimuli are not paired (Holland, 1977). Thus, the difference between the paired and unpaired groups reported by Totty et al (2021) Initial reports suggest a sex difference in this noise-elicited flight behavior such that female rats show more of this behavior than males (Gruene et al, 2015). Within each experiment, we found no such sex differences between male and female mice for the PAR and darting measures of flight behavior, and Totty et al (2021) similarly found no sex differences in such behavior in male and female rats.…”

“…Additionally, there appears to be considerable overlap in the neuroanatomy that supports this circa-strike behavior and fear potentiated startle. Totty et al (2021) found that inactivation of the Central Nucleus or the Bed Nuclei of the Stria Terminalis disrupts the flight response. These two regions have been shown to be important mediators of fear's ability to potentiate startle (e.g., Campeau & Davis, 1995;Davis & Walker, 2014).…”

“…The copyright holder for this preprint this version posted December 6, 2021. ; https://doi.org/10.1101/2021.12.02.470975 doi: bioRxiv preprint salience or intensity of the white noise and does not depend on any particular temporal relation to the US (Hersman et al, 2020). Another recent study using this procedure in rats has suggested that this flight behavior only occurs in context in which fear has been established and is a result of associative processes, but some of the metrics used to score this flight are confounded with any potential freezing prior to the noise presentation (Totty et al, 2021).…”