Temporally precise movement-based predictions in the mouse auditory cortex

Many of the sensations experienced by an organism are caused by their own actions, and accurately anticipating both the sensory features and timing of self-generated stimuli is crucial to a variety of behaviors. In the auditory cortex, neural responses to self-generated sounds exhibit frequency-specific suppression, suggesting that movement-based predictions may be implemented early in sensory processing. Yet it remains unknown whether this modulation results from a behaviorally specific and temporally precise prediction, nor is it known whether corresponding expectation signals are present locally in the auditory cortex. To address these questions, we trained mice to expect the precisely timed acoustic outcome of a forelimb movement using a closed-loop sound-generating lever. Dense neuronal recordings in the auditory cortex revealed suppression of responses to self-generated sounds that was specific to the expected acoustic features, specific to a precise time within the movement, and specific to the movement that was coupled to sound during training. Predictive suppression was concentrated in L2/3 and L5, where deviations from expectation also recruited a population of prediction-error neurons that was otherwise unresponsive. Recording in the absence of sound revealed abundant movement signals in deep layers that were biased toward neurons tuned to the expected sound, as well as temporal expectation signals that were present throughout the cortex and peaked at the time of expected auditory feedback. Together, these findings reveal that predictive processing in the mouse auditory cortex is consistent with a learned internal model linking a specific action to its temporally precise acoustic outcome, while identifying distinct populations of neurons that anticipate expected stimuli and differentially process expected versus unexpected outcomes.