induction of modified fear conditioning in mice for the analysis of flight behavior

Studying Active Defensive Behaviors in Mice with Modified Fear Conditioning

The appropriate selection of defensive behaviors under threatening circumstances is crucial for the survival of all animals. Defensive behaviors gradually shift from one to another based on threat proximity, such as the transition between freezing and flight behaviors1,2,3. Dysregulation of these behaviors is often observed in various mental disorders4. Post-traumatic stress disorder (PTSD) is one such disorder characterized by exaggerated defensive behaviors, like panic responses to non-threatening stimuli4.
Classical fear conditioning in rodents is commonly used as a model for PTSD5,6,7, but rodents do not express flight (panic-like) behaviors in this model8. Consequently, the classical fear conditioning model, often referred to as the &#39;rodent PTSD model,&#39; lacks face validity for PTSD in humans, particularly in capturing flight or panic-like symptoms, which have not been well-studied.
Recently, several modified fear conditioning protocols have successfully demonstrated that rodent subjects exhibit flight behavior during these procedures. For instance, repetitive associations of a conditioned stimulus (CS) and an unconditioned stimulus (US) seven times in a day allowed female rats to exhibit darting behaviors similar to flight behaviors9. In two-day fear conditionings using serial compound stimuli (SCS; composed of tone followed by noise), mice began showing flight behaviors during the noise part of SCS presentations10,11,12. The detailed description of the SCS method is provided in a protocol report13. A three-day fear conditioning with SCS also worked for rats to induce flight behaviors14. However, these new protocols have some limitations. For example, the use of serial cue presentation does not allow for the exclusion of the influence of proximity estimation on defensive behavior. In the case of seven times association of CS-US in rats, the majority of flight responses were observed in females rather than males.
In light of these considerations, we introduce a modified fear conditioning protocol for mice to investigate flight behaviors in a fearful context. Male mice consistently exhibit flight behavior during our modified fear conditioning. In this protocol, the salient tone is used as the CS instead of SCS. Additionally, a minimum of five pairings of CS-US in a day for at least two days, along with fear potentiation by the conditioned context, is required. The protocol provides another option for investigating flight behaviors, complementing previous protocols, depending on the research purpose.

Author Spotlight: Exploring Neural Correlates of Defensive Behaviors in Fear Learning and Extinction

Modified Fear Conditioning for Inducing Flight Behaviors in Mice

Induction of Modified Fear Conditioning in Mice for the Analysis of Flight Behavior

Research

JoVE Journal

Behavior

The appropriate manifestation of defensive behavior in a threatening situation is critical for survival. The prevailing theory suggests that an active ...