Divergent membrane properties of mouse cochlear glial cells around hearing onset

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 Ba 2+ 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.

Functional P2X7Receptors in the Auditory Nerve of Hearing Rodents Localize Exclusively to Peripheral Glia

“…These ranged from extended spindles with small cell bodies, to more complex triangular or multipolar morphologies. Consistent with data from cultured mouse cochlear glia (Smith et al, 2020), the cells identified by S100 immunofluorescence were also labeled by an antibody targeting the transcription factor Sox10 (Fig. 1G).…”

The timing of auditory sensory deficits in Norrie disease has implications for therapeutic intervention

“… 22 ) in mid-modiolar vibratome sections prepared from cochleae of WT and Ndp- KO. At 1 month, using a Tubb3 antibody to label SGNs and a Kir4.1 antibody to label SGCs ( 23 ), there was no difference between the 2 genotypes in the density (number/area) and size of SGNs in basal, middle, or apical cochlear regions ( Figure 3, A–C ). As anti-Tubb3 showed increased background staining of cochlear connective tissue in Ndp -KO mice at 11–12 months (due to immunoreactivity with the secondary antibody targeting mouse IgG; data not shown), we used immunostaining for the neuronal intermediate filament Nf200 ( 24 ) and myelin basic protein (Mbp) to quantify the density and size of SGN cell bodies at this stage ( Figure 3, D–F ).…”

Single-cell transcriptomic profiling of the mouse cochlea: An atlas for targeted therapies

“…We also detected the glial cells, which comprise the satellite glial cells, glial precursor cells, and Schwann cells. The satellite glial cells, that express unique markers different from those expressed in the dorsal root ganglia ( 45 ), encapsulate the soma of spiral ganglion neurons and most likely maintain their excitability ( 46 ). They express genes encoding proteins involved in myelination, such as the myelin oligodendrocyte glycoprotein ( Mog ), myelin-associated glycoprotein ( Mag ), and myelin-associated oligodendrocyte basic protein ( Mobp ).…”