Playback of rat 22-kHz ultrasonic vocalizations as a translational assay of negative affective states: An analysis of evoked behavior and brain activity

Abstract

The subjective nature of human emotions makes them uniquely challenging to investigate in preclinical models. While behavioral assays in rodents aim to evaluate affect (i.e., anxiety, hypervigilance), they often lack ethological validity. Playback of negatively valenced 22-kHz ultrasonic vocalizations (USVs) in rats shows promise as a translational tool to investigate affective processing. Much like how human facial expressions can communicate internal states, rats emit 22-kHz USVs that similarly convey negative affective states to conspecifics indicating possible threat. 22-kHz USV playback elicits avoidance and hypervigilant behaviors, and recruit brain regions comparable to those seen in human brains evoked by viewing fearful faces. Indeed, 22-kHz playback alters neural activity in brain regions associated with negative valence systems (i.e., amygdala, bed nucleus of the stria terminalis, periaqueductal gray) alongside increases in behaviors typically associated with anxiety. Here, we present evidence from the literature that supports leveraging 22-kHz USV playback in rat preclinical models to obtain clinically relevant and translational findings to identify the neural underpinnings of affective processing and neuropathological dysfunction.