Tonotopic differentiation of presynaptic neurotransmitter-releasing machinery in the auditory brainstem during the prehearing period and its selective deficits in Fmr1 knockout mice.
Tonotopic differentiation of presynaptic neurotransmitter-releasing machinery in the auditory brainstem during the prehearing period and its selective deficits in Fmr1 knockout mice.
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DOI：
10.1002/cne.25406
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发表时间：
2022-12
影响因子：
2.5
通讯作者：
Wang, Yuan
中科院分区：
文献类型：
--
作者：
Yu, Xiaoyan;Wang, Yuan
关键词：
音调组织是听觉系统的基本特征。在发育中的听觉脑干中，神经传递的个体发生和成熟沿着音调轴从高频到低频进行。为了探索这种tonotopic发展的潜在机制，我们的目标是确定是否负责神经递质释放的突触前机制是tonotopically分化在发展过程中。在目前的研究中，我们研究了囊泡神经递质转运蛋白和钙传感器，两个中央球员负责加载神经递质到突触囊泡和触发神经递质释放的钙依赖性的方式，分别。使用免疫细胞化学，我们的特点是囊泡谷氨酸转运蛋白（VGLUTs）1和2，囊泡γ-氨基丁酸转运蛋白（VGAT），和钙传感器突触结合蛋白（Syt）1和2在发育中的小鼠内侧核的梯形体（MNTB）的分布模式。我们确定的tonotopic梯度VGLUT 1，VGAT，Syt 1和Syt 2在出生后的第一周，更高的蛋白质密度在更中间（高频）部分的MNTB。这些梯度在听力开始之前逐渐变平。与此相反，VGLUT 2分布相对均匀沿着tonotopic轴在此prehearing期间。在缺乏脆性X智力低下蛋白（一种调节突触发育和可塑性的mRNA结合蛋白）的小鼠中，VGLUT 1、Syt 1和Syt 2的成熟样组织的形成过程发生了改变，但VGAT没有改变。总之，我们的研究结果确定了新的组织模式的选择性突触前蛋白在未成熟的听觉突触，提供了一个潜在的机制，可能有助于tonotopic分化的神经传递在正常和异常的发展。我们确定了五个关键的突触前蛋白质的蛋白质特异性和年龄依赖性tonotopic分布在发展中的听觉脑干和它们的选择性改变在Fmr 1基因敲除小鼠。突触前机制的音调成熟可能为听觉回路正常和异常发育期间神经传递的音调分化提供了潜在的机制。
Tonotopic organization is a fundamental feature of the auditory system. In the developing auditory brainstem, the ontogeny and maturation of neurotransmission progress from high to low frequencies along the tonotopic axis. To explore the underlying mechanism of this tonotopic development, we aim to determine whether the presynaptic machinery responsible for neurotransmitter release is tonotopically differentiated during development. In the current study, we examined vesicular neurotransmitter transporters and calcium sensors, two central players responsible for loading neurotransmitter into synaptic vesicles and for triggering neurotransmitter release in a calcium-dependent manner, respectively. Using immunocytochemistry, we characterized the distribution patterns of vesicular glutamate transporters (VGLUTs) 1 and 2, vesicular gamma-aminobutyric acid transporter (VGAT), and calcium sensor synaptotagmin (Syt) 1 and 2 in the developing mouse medial nucleus of the trapezoid body (MNTB). We identified tonotopic gradients of VGLUT1, VGAT, Syt1, and Syt2 in the first postnatal week, with higher protein densities in the more medial (high-frequency) portion of the MNTB. These gradients gradually flattened before the onset of hearing. In contrast, VGLUT2 was distributed relatively uniformly along the tonotopic axis during this prehearing period. In mice lacking Fragile X mental retardation protein, an mRNA-binding protein that regulates synaptic development and plasticity, progress to achieve the mature-like organization was altered for VGLUT1, Syt1, and Syt2, but not for VGAT. Together, our results identified novel organization patterns of selective presynaptic proteins in immature auditory synapses, providing a potential mechanism that may contribute to tonotopic differentiation of neurotransmission during normal and abnormal development. We identified protein-specific and age-dependent tonotopic distributions of five key presynaptic proteins in the developing auditory brainstem and their selective alterations in Fmr1 KO mice. The tonotopic maturation of the presynaptic machinery may provide a potential mechanism for tonotopic differentiation of neurotransmission during normal and abnormal development of auditory circuits.
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