A Hierarchical Molecular Scaffold for Vestibular Circuit Organization

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Abstract

The vestibular system is essential for balance, posture, gaze stabilization, and spatial orientation, yet lacks the molecular framework that has transformed understanding of other sensory systems. By integrating deep single-cell transcriptomics, spatial mapping, circuit analysis, targeted electrophysiology, and developmental profiling, we identify thirteen vestibular ganglion neuron subtypes and nine hair-cell subtypes, revealing a previously unrecognized degree of cellular diversity within the vestibular periphery. These populations are distributed across distinct epithelial territories and ganglion domains, exhibit stereotyped connectivity patterns, and link molecular identity to distinct intrinsic firing behaviors. Developmental analyses reveal a hierarchical program of vestibular afferent specification in which embryonic meta-identities emerge early, persist into adulthood, and are associated with distinct connectivity patterns, while subtype diversification occurs within these frameworks prior to overt vestibular reflex activity. Together, these findings define the cellular architecture and organizational logic of the vestibular periphery and establish a hierarchical molecular scaffold linking developmental origin, connectivity, and function.

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