# When Silence Breaks: The Influence of Pure Tones and White Noises on Conditioned Flight Responses

## TL;DR

This paper reviews how specific sounds like pure tones and white noise can trigger learned flight responses in mice, offering new insights into fear learning and maladaptive behaviors.

## Contribution

The paper introduces and reviews a novel auditory fear conditioning protocol using serial compound stimuli to elicit learned flight responses in mice.

## Key findings

- A serial compound stimulus (SCS) of pure tone and white noise can induce learned flight responses in mice.
- The SCS protocol provides new insights into the neurobiology of fear learning and maladaptive behaviors.
- The paradigm shows potential for modeling psychiatric conditions like anxiety and PTSD in animal studies.

## Abstract

The flight response is part of the repertoire of adaptive behavioral responses all animals possess and use to face threats coming from their environment. Compared to the other responses, flight requires a high degree of physical effort and is thought to be related to those active coping strategies that can be observed in several psychopathological conditions, including anxiety and depressive disorders. In recent years, a new protocol of auditory fear conditioning has been shown to induce a learned flight response in mice, based on a conditioned stimulus that includes pure tones and white noise, the serial compound stimulus (SCS).

In this review, we examine the effects of stimulus characteristics in fear learning paradigms, particularly in the context of the recently developed SCS paradigm. We will discuss how factors such as conditioned stimulus (CS) modality (e.g., tone versus white noise), stimulus salience, and the temporal relationship between stimuli influence conditioned flight responses.

For the study of both physiological and maladaptive behaviors, fear conditioning still represents the paradigm of choice, e.g., for the modeling of psychiatric conditions such as post‐traumatic stress disorder or phobias. Albeit its relevance in this context, up to now only a few studies have focused on developing procedures for eliciting conditioned flight responses in the laboratory, in favor of freezing/immobilization, the so‐called fright response. The SCS protocol poses new interesting questions on the impact of noises and other stimuli on learning and behavioral responses.

The discovery of SCS already led to interesting findings in the neurobiology of fear learning and shows great potential for the study of maladaptive responses in animal models of psychopathology.

A novel behavioral paradigm by Fadok et al. (2017) pairs a sequence of pure tone and white noise with footshock. After learning, the mouse shows freezing during pure tones and jumps during white noise. This discovery produced shows great potential for the study of fear learning and maladaptive responses.