Task-Dependent and Cell-Type-Specific Modulation of the Mouse Dorsal Cortex of the Inferior Colliculus

Sensory responses in the auditory system are modulated by behavioral context, and this modulation extends as early as the inferior colliculus (IC). Where within the IC it occurs, which neurons it affects, what behavioral variables drive it, and whether it requires the auditory cortex remain unclear. We imaged the dorsal cortex of the IC (DCIC) with two-photon microscopy in head-fixed mice (n = 7) performing a two-alternative forced-choice tone-discrimination task, with blocks of passive listening to the same tones before and after, while recording orofacial movement, licking, and pupil diameter from synchronized video. Unsupervised clustering of sound-evoked responses in 1479 tracked neurons identified four functional response classes: onset-excited, sustained-inhibited, offset/motor-excited, and transient-inhibited. Task engagement modulated these classes in distinct and outcome-dependent ways, with the sustained-inhibited and transient-inhibited classes more suppressed and the offset/motor-excited class more excited during active trials, and with hit and miss trials driving most of the effect. Population activity discriminated active from passive trials above chance, and this discrimination outlasted the stimulus. A linear encoding model attributed a substantial share of the explained variance in three of the four classes to facial movement, whereas pupil diameter contributed little in any class. The correlation between orofacial motion and activity was itself context-dependent in the sustained-inhibited and transient-inhibited classes, but not in the offset/motor-excited class. Bilateral chemogenetic silencing of the auditory cortex (n = 3 mice, 171 matched neurons) altered task modulation only in the sustained-inhibited class. Task-related modulation in the DCIC is therefore heterogeneous across functionally defined neurons, is closely tied to movement, and depends on the auditory cortex in only one of these populations.