Single neuron responses to perceptual difficulty in the mouse auditory cortex

Perceptual learning leads to improvement in behavioral performance, yet how the brain supports challenging perceptual demands is unknown. We used two photon imaging in the mouse primary auditory cortex during behavior in a Go-NoGo task designed to test perceptual difficulty. Using general linear model analysis, we found a subset of neurons that increased their responses during high perceptual demands. Single neurons increased their responses to both Go and NoGo sounds when mice were engaged in the more difficult perceptual discrimination. This increased responsiveness contributes to enhanced cortical network discriminability for the learned sounds. Under passive listening conditions, the same neurons responded weaker to the more similar sound pairs of the difficult task, and the training protocol by itself induced specific suppression to the learned sounds. Our findings identify how neuronal activity in auditory cortex is modulated during high perceptual demands, which is a fundamental feature associated with perceptual improvement.