Cochlear Nuclei Project
Cochlear Nuclei Project
Decipher the Building Blocks of the Mouse Cochlear Nucleus
The cochlear nuclear complex (CN) is the starting point for all central auditory processing and comprises a suite of neuronal cell types that are highly specialized for neural coding of acoustic signals.
To examine how their striking functional specializations are determined at the molecular level, we performed single-nucleus RNA sequencing of the mouse CN to molecularly define all constituent cell types and related them to morphologically- and electrophysiologically-defined neurons using Patch-seq.
We reveal an expanded set of molecular cell types encompassing all previously described major types and discover new subtypes both in terms of topographic and cell-physiologic properties.
Our results define a complete cell-type taxonomy in CN that
reconciles anatomical position, morphological, physiological, and molecular criteria.
This high-resolution account of cellular heterogeneity and specializations from the molecular to the circuit level illustrates molecular underpinnings of functional specializations and enables genetic dissection of auditory processing and hearing disorders with unprecedented specificity.
Distinct Morpho-Electric Cell Types in the CN
(A) Representative morphological reconstructions of each cell type recovered from patch-seq recording in distinct sub-regions of the mouse CN, colored by cell type identity. Dendrites are darker in color; axons are in lighter color. Example membrane responses from four different excitatory (B) and five different inhibitory (C) cell types to 0.6 s-long hyperpolarizing current step and current step at the rheobase (middle two traces), as well as to the current step at 2X rheobase (top trace). Bushy, bushy cells; T-stellate, T stellate cells; Octopus, octopus cells; Fusiform, fusiform cells; Vertica, vertical cells; SSC, superficial stellate cells; Cartwheel, cartwheel cells; D-stellate, D stellate cells; L-stellate, L stellate cells; aVCN, anteroventral cochlear nucleus; pVCN, posteroventral cochlear nucleus; DCN, dorsal cochlear nucleus; OCA, octopus cell area.
Genetic Marker Verification by Immunostaining
Immunostaining for Necab2 (red) in a representative CN sagittal section from GlyT2-EGFP mice