Opposing gradients of ribbon size and AMPA receptor expression underlie sensitivity differences among cochlear-nerve/hair-cell synapses.
Opposing gradients of ribbon size and AMPA receptor expression underlie sensitivity differences among cochlear-nerve/hair-cell synapses.
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DOI：
10.1523/jneurosci.3389-10.2011
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发表时间：
2011-01-19
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影响因子：
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通讯作者：
Liberman MC
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作者：
Liberman LD;Wang H;Liberman MC
听觉系统在跨越六个数量级的输入声压级范围内转换声音诱发的振动。该系统中调节这一令人印象深刻的动态范围的一个重要组成部分存在于耳蜗感觉上皮中，在这里，耳蜗神经纤维的功能亚型在阈值敏感度和自发放电率（SR）上的差异超过1000倍，尽管无论何种类型，每根纤维都通过单个带状突触仅与单个毛细胞接触。为了研究支配单个内毛细胞的5 - 30根初级感觉纤维之间阈值敏感度显著异质性的潜在机制，我们使用对CtBP2（C - 末端结合蛋白2，一种主要的带状蛋白）和GluR2/3（谷氨酸受体2和3）进行免疫染色的小鼠耳蜗的高倍共聚焦成像，对>1200个突触中的突触前带状结构和突触后AMPA受体斑块的大小进行了量化。我们记录到互补的梯度，在耳蜗中部区域最为显著，即来自内毛细胞的轴柱面和/或基极的突触比位于细胞相反区域的突触具有更大的带状结构和更小的受体斑块。AMPA受体表达梯度可能导致了在体时毛细胞两侧所见的耳蜗神经阈值和SR的差异；带状结构大小的差异可能导致了在体外所见的EPSC波形的异质性。
The auditory system transduces sound-evoked vibrations over a range of input sound pressure levels spanning six orders of magnitude. An important component of the system mediating this impressive dynamic range is established in the cochlear sensory epithelium, where functional subtypes of cochlear nerve fibers differ in threshold sensitivity, and spontaneous discharge rate (SR), by more than a factor of 1000, even though, regardless of type, each fiber contacts only a single hair cell via a single ribbon synapse. To study the mechanisms underlying this remarkable heterogeneity in threshold sensitivity among the 5–30 primary sensory fibers innervating a single inner hair cell, we quantified the sizes of presynaptic ribbons and postsynaptic AMPA receptor patches in >1200 synapses, using high-power confocal imaging of mouse cochleas immunostained for CtBP2 (C-terminal binding protein 2, a major ribbon protein) and GluR2/3 (glutamate receptors 2 and 3). We document complementary gradients, most striking in mid-cochlear regions, whereby synapses from the modiolar face and/or basal pole of the inner hair cell have larger ribbons and smaller receptor patches than synapses located in opposite regions of the cell. The AMPA receptor expression gradient likely contributes to the differences in cochlear nerve threshold and SR seen on the two sides of the hair cell in vivo; the differences in ribbon size may contribute to the heterogeneity of EPSC waveforms seen in vitro.