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毛细胞钙通道的门控作用决定着耳蜗神经元的活动。

Gating of hair cell Ca channels governs the activity of cochlear neurons.

作者信息

Karagulyan Nare, Thirumalai Anupriya, Michanski Susann, Qi Yumeng, Fang Qinghua, Wang Haoyu, Ortner Nadine J, Striessnig Jörg, Strenzke Nicola, Wichmann Carolin, Hua Yunfeng, Moser Tobias

机构信息

Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany.

Auditory Neuroscience & Synaptic Nanophysiology Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.

出版信息

Sci Adv. 2025 Jun 20;11(25):eadu7898. doi: 10.1126/sciadv.adu7898. Epub 2025 Jun 18.


DOI:10.1126/sciadv.adu7898
PMID:40532010
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12225641/
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 Ca channel activation among their active zones (AZs), potentially diversifying SGN firing. Here, we tested this hypothesis in mice modeling the human Ca1.3 mutation that causes low-voltage Ca channel activation. We demonstrate activation of Ca influx and glutamate release of IHC AZs at lower voltages, increased spontaneous firing in SGNs, and lower sound threshold of Ca1.3 mice. Loss of synaptic ribbons in IHCs at ambient sound levels of mouse husbandry indicates that low-voltage Ca channel activation poses a risk for noise-induced synaptic damage. We propose that the heterogeneous voltage dependence of Ca1.3 activation among presynaptic IHC AZs contributes to the diversity of firing among the postsynaptic SGNs.

摘要

我们的听觉系统能够处理跨越六个数量级的声音强度。在耳朵中,突触前内毛细胞(IHC)的感受器电位覆盖了整个强度范围,而突触后螺旋神经节神经元(SGN)则通过其放电率编码来划分该范围。IHC在其活性区(AZ)之间改变钙通道激活的电压依赖性,这可能使SGN放电多样化。在这里,我们在模拟导致低电压钙通道激活的人类Ca1.3突变的小鼠中测试了这一假设。我们证明了在较低电压下IHC AZ的钙内流激活和谷氨酸释放,SGN中自发放电增加,以及Ca1.3小鼠的声音阈值降低。在小鼠饲养环境声音水平下,IHC中突触小带的丧失表明低电压钙通道激活对噪声诱导的突触损伤构成风险。我们提出,突触前IHC AZ之间Ca1.3激活的异质电压依赖性有助于突触后SGN之间放电的多样性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3b/12225641/5a58f1e9e2cc/sciadv.adu7898-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3b/12225641/ffd61a53b4c2/sciadv.adu7898-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3b/12225641/f4f35811b274/sciadv.adu7898-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3b/12225641/a77bfcc49269/sciadv.adu7898-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3b/12225641/b4ef0d8b9b23/sciadv.adu7898-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3b/12225641/13b9407085ed/sciadv.adu7898-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3b/12225641/5a58f1e9e2cc/sciadv.adu7898-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3b/12225641/ffd61a53b4c2/sciadv.adu7898-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3b/12225641/f4f35811b274/sciadv.adu7898-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3b/12225641/a77bfcc49269/sciadv.adu7898-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3b/12225641/b4ef0d8b9b23/sciadv.adu7898-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3b/12225641/13b9407085ed/sciadv.adu7898-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3b/12225641/5a58f1e9e2cc/sciadv.adu7898-f6.jpg

相似文献

[1]
Gating of hair cell Ca channels governs the activity of cochlear neurons.

Sci Adv. 2025-6-20

[2]
Bridging the gap between presynaptic hair cell function and neural sound encoding.

Elife. 2024-12-24

[3]
Pou4f1 Defines a Subgroup of Type I Spiral Ganglion Neurons and Is Necessary for Normal Inner Hair Cell Presynaptic Ca Signaling.

J Neurosci. 2019-5-13

[4]
Rab3-interacting molecules 2α and 2β promote the abundance of voltage-gated CaV1.3 Ca2+ channels at hair cell active zones.

Proc Natl Acad Sci U S A. 2015-6-16

[5]
Ca-binding protein 2 inhibits Ca-channel inactivation in mouse inner hair cells.

Proc Natl Acad Sci U S A. 2017-2-28

[6]
The upregulation of K and HCN channels in developing spiral ganglion neurons is mediated by cochlear inner hair cells.

J Physiol. 2024-10

[7]
Hair cells use active zones with different voltage dependence of Ca2+ influx to decompose sounds into complementary neural codes.

Proc Natl Acad Sci U S A. 2016-8-9

[8]
Intrinsic planar polarity mechanisms influence the position-dependent regulation of synapse properties in inner hair cells.

Proc Natl Acad Sci U S A. 2019-4-11

[9]
Concurrent maturation of inner hair cell synaptic Ca2+ influx and auditory nerve spontaneous activity around hearing onset in mice.

J Neurosci. 2013-6-26

[10]
α2δ2 Controls the Function and Trans-Synaptic Coupling of Cav1.3 Channels in Mouse Inner Hair Cells and Is Essential for Normal Hearing.

J Neurosci. 2016-10-26

本文引用的文献

[1]
Noise-induced ribbon synapse loss in the mouse basal cochlear region does not reduce inner hair cell exocytosis.

Front Cell Neurosci. 2025-1-7

[2]
CaBP1 and 2 enable sustained Ca1.3 calcium currents and synaptic transmission in inner hair cells.

Elife. 2024-12-24

[3]
Bridging the gap between presynaptic hair cell function and neural sound encoding.

Elife. 2024-12-24

[4]
A Novel De Novo Gain-of-Function Variant in Neurodevelopmental Disease With Congenital Tremor, Seizures, and Hypotonia.

Neurol Genet. 2024-9-6

[5]
Electron Microscopic Mapping of Mitochondrial Morphology in the Cochlear Nerve Fibers.

J Assoc Res Otolaryngol. 2024-8

[6]
Spatial patterns of noise-induced inner hair cell ribbon loss in the mouse mid-cochlea.

iScience. 2024-1-8

[7]
Diversity matters - extending sound intensity coding by inner hair cells via heterogeneous synapses.

EMBO J. 2023-12-1

[8]
Synaptic activity is not required for establishing heterogeneity of inner hair cell ribbon synapses.

Front Mol Neurosci. 2023-9-6

[9]
The human channel gating-modifying A749G CACNA1D (Cav1.3) variant induces a neurodevelopmental syndrome-like phenotype in mice.

JCI Insight. 2023-10-23

[10]
Molecular signatures define subtypes of auditory afferents with distinct peripheral projection patterns and physiological properties.

Proc Natl Acad Sci U S A. 2023-8

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