New insights from 22-kHz ultrasonic vocalizations to characterize fear responses: relationship with respiration and brain oscillatory dynamics

Abstract Fear behavior depends on interactions between the medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA), and the expression of fear involves synchronized activity in theta and gamma oscillatory activities. In addition, freezing, the most classical measure of fear response in rodents, temporally coincides with the development of sustained 4-Hz oscillations in prefrontal–amygdala circuits. Interestingly, these oscillations were recently shown to depend on the animal’s respiratory rhythm, supporting the growing body of evidence pinpointing the influence of nasal breathing on brain rhythms. During fearful states, rats also emit 22-kHz ultrasonic vocalizations (USV) which drastically affect respiratory rhythm. However, the relationship between 22-kHz USV, respiration and brain oscillatory activities is still unknown. Yet such information is crucial for a comprehensive understanding of how the different components of fear response collectively modulate rat’s brain neural dynamics. Here we trained male rats in an odor fear conditioning task, while recording simultaneously local field potentials in BLA, mPFC and olfactory piriform cortex, together with USV calls and respiration. We show that USV calls coincide with an increase in delta and gamma power and a decrease in theta power. In addition, during USV emission in contrast to silent freezing, there is no coupling between respiratory rate and delta frequency, and the modulation of fast oscillations amplitude relative to the phase of respiration is modified. We propose that sequences of USV calls could result in a differential gating of information within the network of structures sustaining fear behavior, thus potentially modulating fear expression/memory. Significance Statement While freezing is the most frequently used measure of fear, it is only one amongst the different components of rodents’ response to threatening events. USV is another index that gives additional insight into the socioemotional status of an individual. Our study is the first to describe the effects of USV production on rat’s brain oscillatory activities in the fear neural network, and to relate some of them to changes in nasal breathing. A better knowledge of the impact of social vocalizations on brain neural dynamics is not only important for understanding the respective weight of the different components of fear response, but is also particularly relevant for rodent models of human neuropsychiatric disorders, for which socio-affective communication is severely impaired.