Molecular and cell type-specific determinants of inferior colliculus development and auditory function

Sound perception requires sensory information processing through brain regions where alterations to cellular composition or function may impact auditory-relevant behaviors. The inferior colliculus (IC) is a central midbrain hub for integrating and transforming auditory information prior to relay to the forebrain. However, the molecular logic that underlies the cell type specification of the IC remains unknown. Here, using a multiomic approach, we define the transcriptional and chromatin landscapes that underlie IC cell type diversity. We identify distinct glutamatergic neuronal subclasses and the gene regulatory programs that drive their specification, maturation, and survival. We show that perturbation to the transcription factor FOXP2, previously implicated in speech and language as well as brain disorders with altered sensory processing, selectively disrupts the specification and survival of three newly defined glutamatergic neuronal subclasses. We link these molecular and cellular disruptions to functional deficits in auditory processing including altered brainstem and forebrain responses and impaired behavioral sensitivity to acoustic stimuli. Together, these results link gene regulatory mechanisms to cell type-specification in the IC, providing insight into how molecular control of neuronal identity in midbrain sensory centers contributes to systems-level processing of sound.