| First Author | Conrad LJ | Year | 2024 |
| Journal | J Physiol | Volume | 602 |
| Issue | 20 | Pages | 5329-5351 |
| PubMed ID | 39324853 | Mgi Jnum | J:355459 |
| Mgi Id | MGI:7748841 | Doi | 10.1113/JP286134 |
| Citation | Conrad LJ, et al. (2024) The upregulation of K(+) and HCN channels in developing spiral ganglion neurons is mediated by cochlear inner hair cells. J Physiol 602(20):5329-5351 |
| abstractText | Spiral ganglion neurons (SGNs) are primary sensory afferent neurons that relay acoustic information from the cochlear inner hair cells (IHCs) to the brainstem. The response properties of different SGNs diverge to represent a wide range of sound intensities in an action-potential code. This biophysical heterogeneity is established during pre-hearing stages of development, a time when IHCs fire spontaneous Ca(2+) action potentials that drive glutamate release from their ribbon synapses onto the SGN terminals. The role of spontaneous IHC activity in the refinement of SGN characteristics is still largely unknown. Using pre-hearing otoferlin knockout mice (Otof(-/-)), in which Ca(2+)-dependent exocytosis in IHCs is abolished, we found that developing SGNs fail to upregulate low-voltage-activated K(+)-channels and hyperpolarisation-activated cyclic-nucleotide-gated channels. This delayed maturation resulted in hyperexcitable SGNs with immature firing characteristics. We have also shown that SGNs that synapse with the pillar side of the IHCs selectively express a resurgent K(+) current, highlighting a novel biophysical marker for these neurons. RNA-sequencing showed that several K(+) channels are downregulated in Otof(-/-) mice, further supporting the electrophysiological recordings. Our data demonstrate that spontaneous Ca(2+)-dependent activity in pre-hearing IHCs regulates some of the key biophysical and molecular features of the developing SGNs. KEY POINTS: Ca(2+)-dependent exocytosis in inner hair cells (IHCs) is otoferlin-dependent as early as postnatal day 1. A lack of otoferlin in IHCs affects potassium channel expression in SGNs. The absence of otoferlin is associated with SGN hyperexcitability. We propose that type I spiral ganglion neuron functional maturation depends on IHC exocytosis. |
