The mammalian auditory system encodes sounds with subtypes of spiral ganglion neurons (SGNs) that differ in sound level sensitivity, permitting discrimination across a wide range of levels. Recent work suggests the physiologically-defined SGN subtypes correspond to at least three molecular subtypes. It is not known how information from the different subtypes converges within the cochlear nucleus. We examined this issue using transgenic mice of both sexes that express Cre recombinase in SGNs that are positive for markers of two of these subtypes: CALB2 (calretinin) in type 1a SGNs, and LYPD1 in type 1c SGNs, which correspond to high- and low-sensitivity subtypes, respectively. We crossed these with mice expressing floxxed channelrhodopsin, which allowed specific activation of axons from type 1a or 1c SGNs using optogenetics. We made voltage-clamp recordings from bushy cells in the anteroventral cochlear nucleus (AVCN) and found that the synapses formed by CALB2- and LYPD1-positive SGNs had similar EPSC amplitudes and short-term plasticity. Immunohistochemistry revealed that individual bushy cells receive a mix of 1a, 1b, and 1c synapses with VGluT1-positive puncta of similar sizes. We used optogenetic stimulation during in vivo recordings to classify chopper and primary-like units as receiving vs. not-receiving 1a- or 1c-type inputs. These groups showed no significant difference in threshold or spontaneous rate, suggesting the subtypes do not segregate into distinct processing streams in the AVCN. Our results indicate that principal cells in the AVCN integrate information from all SGN subtypes with extensive convergence, which could optimize sound encoding across a large dynamic range.Significance statement Sound information is carried to the brain by auditory afferents that differ in their sensitivity to sound. Auditory afferents fall into three subtypes differing in their spontaneous and sound-evoked activity. These subtypes can be distinguished by anatomical, physiological, and molecular features. However, it is not well understood how the three subtypes relay information to the brain. We addressed this question using optogenetic stimulation to study the properties of two afferent subtypes in the anteroventral part of the cochlear nucleus. We found that the properties of synapses are indistinguishable between subtypes, and they show extensive convergence, suggesting that combining inputs with different sound level sensitivity is important for processing sound.

中文翻译：

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1 型螺旋神经节神经元亚型会聚到前腹侧耳蜗核的主要神经元上。


哺乳动物听觉系统使用螺旋神经节神经元 （SGN） 亚型编码声音，这些亚型在声级灵敏度上有所不同，从而可以在广泛的级别范围内进行区分。最近的研究表明，生理学定义的 SGN 亚型对应于至少三种分子亚型。目前尚不清楚来自不同亚型的信息如何在耳蜗核内汇聚。我们使用在对其中两种亚型的标志物呈阳性的 SGN 中表达 Cre 重组酶的两性转基因小鼠来研究这个问题：1a 型 SGN 中的 CALB2（钙调蛋白）和 1c SGN 中的 LYPD1，分别对应于高敏和低敏亚型。我们将这些与表达 floxxed 通道视紫红质的小鼠杂交，这允许使用光遗传学特异性激活来自 1a 或 1c SGN 的轴突。我们对前腹侧耳蜗核 （AVCN） 中的浓密细胞进行了电压钳记录，发现由 CALB2 和 LYPD1 阳性 SGN 形成的突触具有相似的 EPSC 振幅和短期可塑性。免疫组化显示，单个浓密细胞接收 1a、1b 和 1c 突触与相似大小的 VGluT1 阳性点的混合物。我们在体内记录过程中使用光遗传学刺激将斩波器和初级样单元分类为接收与未接收 1a 或 1c 型输入。这些组在阈值或自发率方面没有显著差异，表明亚型在 AVCN 中没有分离成不同的处理流。我们的结果表明，AVCN 中的主细胞以广泛的收敛性整合了来自所有 SGN 亚型的信息，这可以在较大的动态范围内优化声音编码。意义陈述 声音信息由听觉传入神经传递到大脑，这些传入神经对声音的敏感性不同。听觉传入神经分为三个亚型，它们的自发活动和声音诱发活动不同。这些亚型可以通过解剖学、生理学和分子学特征来区分。然而，目前尚不清楚这三种亚型如何将信息传递到大脑。我们使用光遗传学刺激来解决这个问题，以研究耳蜗核前腹侧部分两种传入亚型的特性。我们发现突触的特性在亚型之间无法区分，并且它们显示出广泛的收敛性，这表明将具有不同声级灵敏度的输入组合在一起对于处理声音很重要。