Comprehensively defining cellular specializations for initiating parallel auditory pathways in the mouse cochlear nucleus.

The cochlear nucleus (CN), the starting point for all central auditory processing, comprises a suite of neuronal cell types that are morphologically and biophysically specialized for initiating parallel pathways, yet their molecular distinctions are largely unknown. To determine how functional specialization is defined at the molecular level, we employed a single-nucleus RNA sequencing analysis of the mouse CN to molecularly define its constituent cell types and then related them to well-established cell types with classical approaches. We reveal a one-to-one correspondence between molecular cell types and all previously described major types, defining a cell-type taxonomy that meaningfully reconciles anatomical position, morphological, physiological, and molecular criteria. Our approach also yields continuous and/or discrete molecular distinctions within several major principal cell types that account for hitherto unresolved distinctions in their anatomical position, morphology, and physiology. This study thus provides a higher-resolution and thoroughly validated account of cellular heterogeneity and specializations in the CN from the molecular to the circuit level, opening a new window for genetic dissection of auditory processing and hearing disorders with unprecedented specificity.