Wong Nicole F, Brongo Sydney E, Forero Evan A, Sun Shuohao, Cook Connor J, Lauer Amanda M, Müller Ulrich, Xu-Friedman Matthew A
Department of Biological Sciences, University at Buffalo, State University of New York, Buffalo, New York 14260.
The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Neurosci. 2025 Feb 5;45(6):e1507242024. doi: 10.1523/JNEUROSCI.1507-24.2024.
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 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 floxed 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 versus nonreceiving 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.
哺乳动物听觉系统通过螺旋神经节神经元(SGNs)的亚型对声音进行编码,这些亚型在声音水平敏感性方面存在差异,从而能够在广泛的声音水平范围内进行区分。最近的研究表明,生理学定义的SGN亚型至少对应三种分子亚型。目前尚不清楚来自不同亚型的信息如何在耳蜗核内汇聚。我们使用了在两种亚型标记物呈阳性的SGNs中表达Cre重组酶的两性转基因小鼠来研究这个问题:1a型SGNs中的CALB2(钙视网膜蛋白)和1c型SGNs中的LYPD1,它们分别对应高敏感性和低敏感性亚型。我们将这些小鼠与表达floxed通道视紫红质的小鼠杂交,这使得能够使用光遗传学特异性激活1a型或1c型SGNs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SGNs形成的突触具有相似的兴奋性突触后电流(EPSC)幅度和短期可塑性。免疫组织化学显示,单个浓密细胞接收1a、1b和1c突触的混合输入,其VGluT1阳性突触小体大小相似。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位分类为接收或不接收1a型或1c型输入。这些组在阈值或自发率上没有显著差异,这表明这些亚型在AVCN中不会分离成不同的处理流。我们的结果表明,AVCN中的主要细胞通过广泛的汇聚整合来自所有SGN亚型的信息,这可以在大动态范围内优化声音编码。