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.
