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体外培养条件下，听觉毛细胞和螺旋神经节神经元可再生具有精细释放特性的突触。

Auditory hair cells and spiral ganglion neurons regenerate synapses with refined release properties in vitro.

机构信息

The Center for Hearing and Balance, The Johns Hopkins School of Medicine, Baltimore, MD 21205.

Department of Otolaryngology Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, MD 21205.

出版信息

Proc Natl Acad Sci U S A. 2024 Jul 30;121(31):e2315599121. doi: 10.1073/pnas.2315599121. Epub 2024 Jul 26.

DOI:10.1073/pnas.2315599121
PMID:39058581
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11294990/
Abstract

Ribbon synapses between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs) in the inner ear are damaged by noise trauma and with aging, causing "synaptopathy" and hearing loss. Cocultures of neonatal denervated organs of Corti and newly introduced SGNs have been developed to find strategies for improving IHC synapse regeneration, but evidence of the physiological normality of regenerated synapses is missing. This study utilizes IHC optogenetic stimulation and SGN recordings, showing that, when P3-5 denervated organs of Corti are cocultured with SGNs, newly formed IHC/SGN synapses are indeed functional, exhibiting glutamatergic excitatory postsynaptic currents. When using older organs of Corti at P10-11, synaptic activity probed by deconvolution showed more mature release properties, closer to the specialized mode of IHC synaptic transmission crucial for coding the sound signal. This functional assessment of newly formed IHC synapses developed here, provides a powerful tool for testing approaches to improve synapse regeneration.

摘要

内耳中内毛细胞 (IHC) 和 I 型螺旋神经节神经元 (SGN) 之间的带状突触会因噪声创伤和衰老而受损，导致“突触病”和听力损失。已经开发出新生去神经耳蜗器官和新引入的 SGN 的共培养物，以寻找改善 IHC 突触再生的策略，但再生突触的生理正常性的证据尚缺乏。本研究利用 IHC 光遗传刺激和 SGN 记录，表明当 P3-5 去神经耳蜗器官与 SGN 共培养时，新形成的 IHC/SGN 突触确实具有功能，表现出谷氨酸能兴奋性突触后电流。当使用 P10-11 时的较老的耳蜗器官时，通过反卷积探测的突触活性显示出更成熟的释放特性，更接近对声音信号编码至关重要的 IHC 突触传递的专门模式。这里开发的对新形成的 IHC 突触的功能评估为改善突触再生的方法提供了强大的测试工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e5d/11294990/04ab65238a0a/pnas.2315599121fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e5d/11294990/035b52c462be/pnas.2315599121fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e5d/11294990/0b4564a3fea5/pnas.2315599121fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e5d/11294990/8c580f8af6ae/pnas.2315599121fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e5d/11294990/1ac48bb9f603/pnas.2315599121fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e5d/11294990/04ab65238a0a/pnas.2315599121fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e5d/11294990/035b52c462be/pnas.2315599121fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e5d/11294990/0b4564a3fea5/pnas.2315599121fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e5d/11294990/8c580f8af6ae/pnas.2315599121fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e5d/11294990/1ac48bb9f603/pnas.2315599121fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e5d/11294990/04ab65238a0a/pnas.2315599121fig05.jpg

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本文引用的文献

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Sci Rep. 2023 Nov 9;13(1):19456. doi: 10.1038/s41598-023-46859-6.
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Round-window delivery of lithium chloride regenerates cochlear synapses damaged by noise-induced excitotoxic trauma via inhibition of the NMDA receptor in the rat.圆窗内给予氯化锂通过抑制 NMDA 受体可使噪声损伤的大鼠耳蜗突触再生。
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Optogenetics and electron tomography for structure-function analysis of cochlear ribbon synapses.
光遗传学和电子断层扫描技术在耳蜗带状突触结构功能分析中的应用。
Elife. 2022 Dec 23;11:e79494. doi: 10.7554/eLife.79494.
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Neuronal Redevelopment and the Regeneration of Neuromodulatory Axons in the Adult Mammalian Central Nervous System.成年哺乳动物中枢神经系统中神经元的重新发育和神经调节轴突的再生
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The Cl-channel TMEM16A is involved in the generation of cochlear Ca waves and promotes the refinement of auditory brainstem networks in mice.氯离子通道 TMEM16A 参与耳蜗 Ca 波的产生，并促进小鼠听觉脑干网络的精细化。
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A Genetic modification that reduces ON-bipolar cells in hESC-derived retinas enhances functional integration after transplantation.一种减少人胚胎干细胞来源视网膜中ON双极细胞的基因改造可增强移植后的功能整合。
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