Experience-dependent flexibility in a molecularly diverse central-to-peripheral auditory feedback system.
Experience-dependent flexibility in a molecularly diverse central-to-peripheral auditory feedback system.
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DOI：
10.7554/elife.83855
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发表时间：
2023-03-06
期刊：
影响因子：
7.7
通讯作者：
Goodrich LV
中科院分区：
文献类型：
--
作者：
Frank MM;Sitko AA;Suthakar K;Torres Cadenas L;Hunt M;Yuk MC;Weisz CJC;Goodrich LV
脑干橄榄耳蜗神经元（OCN）通过反馈投射到耳蜗来调节听觉处理的最早阶段，并已被证明可以影响听力并保护耳朵免受声音引起的损伤。在这里，我们使用单核测序，解剖重建，和电生理学的特点，在出生后的发展，在成熟的动物，和声音暴露后的小鼠OCN。我们确定了已知内侧（MOC）和外侧（OCN）亚型的标记物，并表明它们表达随发育而变化的生理相关基因的不同队列。此外，我们还发现了一种富含神经肽的神经肽亚型，它能产生神经肽Y沿着其他神经递质。在整个耳蜗中，这两种亚型都在宽的频域上延伸分支。此外，听觉损伤后，耳蜗神经肽表达强烈上调，可能为耳蜗提供持续的保护信号。因此，OCN有望在从毫秒到几天的时间尺度上对早期听觉处理产生扩散的动态影响。就像我们的瞳孔会根据我们眼睛所能获得的光量而扩大或缩小一样，我们的耳朵也会根据我们所遇到的声音环境来调整它们的灵敏度。有证据表明，一组被称为橄榄耳蜗神经元（简称OCN）的细胞可能参与了这一过程。这些细胞位于脑干中，但投射到耳蜗中，耳蜗是将声波转化为传递到大脑的电脉冲的内耳结构。OCN可能会调节声音是如何被检测和编码的。“从历史上看，OCN根据不同的形态和在听力中的作用分为两组（内侧或外侧OCN）。例如，内侧OCN被认为通过向放大某些听觉信号的内耳细胞发送分子信号来保护我们的耳朵免受响亮的声音。然而，仍然很难解开不同类型OCN的精确功能，部分原因是科学家仍然缺乏标记物，使他们能够简单地根据遗传活性区分内侧和外侧细胞。Frank等人旨在通过确定哪些基因被打开以及在个体小鼠内侧和外侧OCN中打开的程度来消除这一瓶颈;这是在整个发育过程中以及暴露于巨大噪音后完成的。实验发现了内侧和外侧OCN的一系列遗传标记，表明这些细胞开启与其在发育过程中的作用相关的不同基因组。该基因表达数据还显示，存在两组不同的外侧OCN，其中一组的特征在于产生大量神经肽，这是一种可以调节神经回路活动的化学信使。在发育中和成年小鼠中的进一步研究表明，这种生产是由细胞的活动塑造的，当动物暴露于破坏性的噪音水平时，神经肽水平会增加。这种变化会持续几天，这表明这种经历会对大脑如何向耳朵提供反馈产生长期影响。总的来说，Frank等人的研究结果将有助于更好地识别和描述不同类型的OCN及其在听力中的作用。通过揭示介导对大声噪音反应的化学信使，这项研究可能有助于更好地了解如何预防或减少听力损失。
Brainstem olivocochlear neurons (OCNs) modulate the earliest stages of auditory processing through feedback projections to the cochlea and have been shown to influence hearing and protect the ear from sound-induced damage. Here, we used single-nucleus sequencing, anatomical reconstructions, and electrophysiology to characterize murine OCNs during postnatal development, in mature animals, and after sound exposure. We identified markers for known medial (MOC) and lateral (LOC) OCN subtypes, and show that they express distinct cohorts of physiologically relevant genes that change over development. In addition, we discovered a neuropeptide-enriched LOC subtype that produces Neuropeptide Y along with other neurotransmitters. Throughout the cochlea, both LOC subtypes extend arborizations over wide frequency domains. Moreover, LOC neuropeptide expression is strongly upregulated days after acoustic trauma, potentially providing a sustained protective signal to the cochlea. OCNs are therefore poised to have diffuse, dynamic effects on early auditory processing over timescales ranging from milliseconds to days. Just as our pupils dilate or shrink depending on the amount of light available to our eyes, our ears adjust their sensitivity based on the sound environment we encounter. Evidence suggests that a group of cells known as olivocochlear neurons (OCNs for short) may be involved in this process. These cells are located in the brainstem but project into the cochlea, the inner ear structure that converts sound waves into the electrical impulses relayed to the brain. OCNs may mediate how sounds are detected and encoded "at the source." Historically, OCNs have been divided into two groups (medial or lateral OCNs) based on different morphologies and roles in hearing. For instance, medial OCNs are thought to protect our ears against loud sounds by sending molecular signals to the inner ear cells that amplify certain auditory signals. However, it remains difficult to disentangle the precise function of the different types of OCNs, in part because scientists still lack markers that would allow them to distinguish between medial and lateral cells simply based on genetic activity. Frank et al. aimed to eliminate this bottleneck by identifying which genes were switched on and to what degree in individual mouse medial and lateral OCNs; this was done throughout development and after exposure to loud noises. The experiments uncovered a range of genetic markers for medial and lateral OCNs, showing that these cells switch on different sets of genes relevant to their role over development. This gene expression data also revealed that two distinct groups of lateral OCNs exist, one of which is characterised by the production of large amounts of neuropeptides, a type of chemical messenger that can modulate neural circuit activity. Further work in both developing and adult mice showed that this production is shaped by the activity of the cells, with the neuropeptide levels increasing when the animals are exposed to damaging levels of noise. This change lasts for several days, suggesting that such an experience can have long-lasting effects on how the brain provides feedback to the ear. Overall, the results by Frank et al. will help to better identify and characterize the different types of OCNs and the role that they have in hearing. By uncovering the chemical messengers that mediate the response to loud noises, this research may contribute to a better understanding of how to prevent or reduce hearing loss.