Sunday, June 1, 2025
6/1/2025
Long-range exchange of expectation, experience and error during auditory-motor learning - Project Summary Many of the sensations we perceive are caused by our own actions, which we can distinguish from externally generated stimuli. In the auditory system, the ability to differentiate between external and self-generated sounds is crucial for functions such as vocal communication, musical training and general auditory perception. The tight correlation between motor-related signals, or corollary discharge, and the timing of incoming sensory information is leveraged by the auditory system to discern that a given sound is self-generated. Throughout our lifespan, we learn that certain movements predictably elicit reproducible sounds. However, in different contextual settings, the same movements can yield novel sounds that violate expectations from our previous experiences, and we must update our predictions about the sensory consequences of our actions. Neural responses in sensory regions of the brain are sensitive to expectations, such that expected self-generated sounds are suppressed in the primary auditory cortex (A1) and unexpected sounds elicit responses from “prediction error” neurons. The predictive suppression of expected self-generated sounds in A1 is mediated by secondary motor cortex (M2) inputs to A1 neurons, which serve as a potential source for establishing specific associations between sounds and their corresponding movements. However, the function of prediction error signals and the mechanisms underlying their utilization in generating neuronal representations for newly encountered self-generated sounds remains unclear. The primary objective of this project is to integrate quantitative behavior, cellular imaging, and circuit perturbations to examine how coordinated activity between the motor and auditory cortices encodes movements with various acoustic outcomes and tests the hypothesis that corollary discharge signals do not simply encode action, but instead convey rich information to sensory cortex about movements and their expected acoustic consequences. Specifically, we will utilize chronic two-photon (2P) calcium imaging to examine the response patterns of neuronal ensembles in M2 as mice acquire the association between a lever-pressing behavior and an accompanying sound. Through changing the sound associated with the lever-press movement, we will assess the plasticity and reorganization of these circuits as mice learn a new self-generated sound (Aim 1). To further explore the role of the motor cortex in encoding movement with its sensory consequences, we will employ a chemogenetic approach to selectively inhibit M2 activity at various stages of learning new acoustic associations and evaluate whether novel sounds can eventually be suppressed in the auditory cortex (Aim 2). Lastly, we aim to determine whether M2 selectively communicates sound-related corollary discharge signals to A1 relative to other sensory cortices. (Aim 3). Overall, these experiments will provide valuable insights into the brain’s mechanisms for predicting and updating the acoustic consequences of our actions in real time and could uncover fundamental principles underlying the dynamic information flow between sensory and motor regions of the brain.
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