Pupil-linked arousal differentially modulates cell-type-specific sensory processing

Abstract Arousal is a ubiquitous influence on the brain that fluctuates during wakefulness and modulates sensation and perception. These fluctuations impact membrane potential, cortical state, and sensory encoding, yet prior studies report inconsistent effects, likely due to averaging across heterogeneous cell types. To resolve this, we combined two-photon calcium imaging and pupillometry in awake mice to examine arousal-related activity in excitatory subpopulations of the auditory cortex: intratelencephalic (IT), extratelencephalic (ET), and corticothalamic (CT) neurons. Pupil-linked arousal modulated all cell types through diverse linear and non-linear response motifs. ET neurons showed significant multiplicative and additive gain modulation, with enhanced response magnitude and encoding but reduced frequency selectivity. CT and L2/3 neurons exhibited inverted-U relationships between arousal and both response strength and decoding accuracy, while IT neurons were minimally affected. These patterns closely tracked changes in population-level reliability, revealing a mechanistic link between internal state and the stability of sensory representations. Competing Interest Statement The authors have declared no competing interest.