Morphological analysis of glia-neuron interactions during cochlea wiring

Abstract

Cochlea hair cells, the sensory receptors for hearing, transduce auditory input to electrical signal relayed to the brain via bipolar spiral ganglion neurons (SGNs). SGNs extend a peripheral process (SGNpp) to target one hair cell, and their central processes coalesce with vestibular axons and brainstem efferents to form the eighth cranial nerve. In the mature cochlea, SGN cell bodies are myelinated by satellite glia while SGN peripheral and central axons are myelinated by Schwann cells. SGNpps exit the spiral ganglion at the same time as neural crest-derived glia precursors (GPs) and, after reaching the hair cell region, SGNpps of similar characteristic sound frequency will fasciculate into radial bundles intertwined with GPs. It is not known how radial bundles are formed nor if the tightly associated GPs contribute to SGNpp outgrowth organization during cochlear wiring. Here we find that GPs extend radially ordered “sawtooth-like” protrusions at the early stage of SGNpp extension. Most SGNpps can be found growing along or behind the glia protrusions, within the same radial domain. This suggests that GPs may play a role in early SGNpp pathfinding. From sparse labeling of GPs early in development, we identified four morphological classes of GPs across the cochlea. These morphologies hint at multiple modes of interaction with SGNpps, other migrating GPs and otic mesenchyme cells that may foster cochlea wiring fidelity. Furthermore, changing interactions between GPs and SGNpps during development may promote radial bundling of SGNpps underlying cochlear tonotopy.