Divergent membrane properties of mouse cochlear glial cells around hearing onset.

Katie E Smith,Phoebe Murphy,Daniel J Jagger

doi:10.1002/jnr.24744

Abstract

Spiral ganglion neurons (SGNs) are the primary afferent neurons of the auditory system, and together with their attendant glia, form the auditory nerve. Within the cochlea, satellite glial cells (SGCs) encapsulate the cell body of SGNs, whereas Schwann cells (SCs) wrap their peripherally- and centrally-directed neurites. Despite their likely importance in auditory nerve function and homeostasis, the physiological properties of auditory glial cells have evaded description. Here, we characterized the voltage-activated membrane currents of glial cells from the mouse cochlea. We identified a prominent weak inwardly rectifying current in SGCs within cochlear slice preparations (postnatal day P5-P6), which was also present in presumptive SGCs within dissociated cultures prepared from the cochleae of hearing mice (P14-P15). Pharmacological block by Ba2+ and desipramine suggested that channels belonging to the Kir4 family mediated the weak inwardly rectifying current, and post hoc immunofluorescence implicated the involvement of Kir4.1 subunits. Additional electrophysiological profiles were identified for glial cells within dissociated cultures, suggesting that glial subtypes may have specific membrane properties to support distinct physiological roles. Immunofluorescence using fixed cochlear sections revealed that although Kir4.1 is restricted to SGCs after the onset of hearing, these channels are more widely distributed within the glial population earlier in postnatal development (i.e., within both SGCs and SCs). The decrease in Kir4.1 immunofluorescence during SC maturation was coincident with a reduction of Sox2 expression and advancing neurite myelination. The data suggest a diversification of glial properties occurs in preparation for sound-driven activity in the auditory nerve.

Highlights

Spiral ganglion neurons (SGNs) transmit acoustic information from sensory hair cells in the cochlear periphery to central neurons in the brainstem
Three broad classes of peripheral glia are associated with SGNs: (a) satellite glial cells (SGCs) which wrap around the neuronal cell body, plus (b) myelinating and (c) non-myelinating Schwann cells (SCs) which associate with the neurites of type I and type II SGNs, respectively
Multiple layers of compact myelin originating from SCs wrap the neurites of type I SGNs, whereas fewer, more loosely assembled myelin layers originating from SGCs surround the neuronal cell body (Rosenbluth, 1962)

Summary

| INTRODUCTION

Spiral ganglion neurons (SGNs) transmit acoustic information from sensory hair cells in the cochlear periphery to central neurons in the brainstem. Mutations in the MPZ or PMP22 genes that encode specific PNS myelin proteins (Greenfield et al, 1973; Lemke & Axel, 1985; Snipes et al, 1992) are associated with auditory neuropathies (Kabzinska et al, 2007; Kovach et al, 2002; Starr et al, 2003; Verhagen et al, 2005) Together, these observations highlight the importance of myelin formation and its maintenance by SCs and SGCs in the auditory periphery. | 3 distributed in glial cells during the first postnatal week, but decreased in SCs only as myelination advanced These results suggest that the membrane properties of SGCs and SCs undergo a profound diversification during cochlear maturation, which may reflect regional functional specializations contributing to normal hearing

| MATERIALS AND METHODS

Findings

| DISCUSSION