Pupil-linked arousal heterogeneously modulates cell-type–specific sensory processing

Arousal is a ubiquitous influence on the brain. It affects membrane potentials, cortical state, and sensory encoding, yet how arousal influences distinct excitatory cell types in neocortex remains poorly understood. To test this, we combined two-photon calcium imaging and pupillometry in awake mice to examine arousal-related activity in excitatory subpopulations of auditory cortex: intratelencephalic (IT), extratelencephalic (ET), and corticothalamic (CT) neurons. We observed substantial within-group variability alongside significant cell-type-specific differences, suggesting that arousal exerts a widespread but heterogeneous influence on cortical excitatory networks. Pupil-linked arousal modulated subtypes through linear and nonlinear response motifs. ET neurons exhibited predominantly multiplicative and additive gain modulations, with enhanced response magnitude and stimulus encoding but reduced frequency selectivity. CT and layer 2/3 neurons showed inverted-U relationships between arousal and response strength and decoding accuracy, whereas IT neurons were minimally affected. These effects tracked changes in population-level reliability, revealing a mechanistic link between internal state and representational stability.