A naturalistic assay for measuring behavioral responses to aversive stimuli at millisecond timescale

Abstract

AbstractWe have designed a Virtual Burrow Assay (VBA) to detect the behavioral responses of head-fixed mice to aversive stimuli. We demonstrate its suitability for measuring novelty detection as well as aversion to both conditioned and innately aversive cues. The VBA simulates a scenario in which a mouse, poised at the threshold of its burrow, evaluates whether to remain exposed to potential threats outside or to retreat inside an enclosure. When presented with aversive stimuli, mice exhibit a stereotyped retreat whose onset is determined by measuring the position of a moveable burrow. This withdrawal, which requires no training, is characterized by an abrupt transition that unfolds within milliseconds—a timescale similar to that of neuronal dynamics, permitting direct comparison between the two. The assay is compatible with standard electrophysiological and optical methods for measuring and perturbing neuronal activity.