Authors
Karagulyan N, Thirumalai A, Michanski S, Qi Y, Fang Q, Wang H, Ortner NJ, Striessnig J, Strenzke N, Wichmann C, Hua Y, Moser T
Journal
Science Advances
Citation
Sci Adv. 2025 Jun 20;11(25):eadu7898.
Abstract
Our sense of hearing processes sound intensities spanning six orders of magnitude. In the ear, the receptor potential of presynaptic inner hair cells (IHCs) covers the entire intensity range, while postsynaptic spiral ganglion neurons (SGNs) tile the range with their firing rate codes. IHCs vary the voltage dependence of Ca2+ channel activation among their active zones (AZs), potentially diversifying SGN firing. Here, we tested this hypothesis in mice modeling the human CaV1.3A749G mutation that causes low-voltage Ca2+ channel activation. We demonstrate activation of Ca2+ influx and glutamate release of IHC AZs at lower voltages, increased spontaneous firing in SGNs, and lower sound threshold of CaV1.3A749G/A749G mice. Loss of synaptic ribbons in IHCs at ambient sound levels of mouse husbandry indicates that low-voltage Ca2+ channel activation poses a risk for noise-induced synaptic damage. We propose that the heterogeneous voltage dependence of CaV1.3 activation among presynaptic IHC AZs contributes to the diversity of firing among the postsynaptic SGNs.
