Maintenance of neuronal size gradient in MNTB requires sound-evoked activity
Maintenance of neuronal size gradient in MNTB requires sound-evoked activity
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DOI：
10.1152/jn.00528.2016
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发表时间：
2017-02-01
影响因子：
2.5
通讯作者：
Tempel, Bruce L.
中科院分区：
文献类型：
--
作者：
Weatherstone, Jessica H.;Kopp-Scheinpflug, Conny;Tempel, Bruce L.
斜方体内侧核（MNTB）是声音位置计算过程中抑制的重要来源。它以高频率传输快速和精确定时的动作电位;这需要有效的钙清除机制，其中质膜钙ATP酶2（PMCA 2）是关键组分。Deafwaddler（dfw（2 J））突变小鼠在PMCA 2中具有无效突变，导致纯合子耳聋（dfw（2 J）/dfw（2 J））和杂合子高频听力损失（+/dfw（2 J））。尽管耳聋表型，在dfw 2 J纯合突变体中未观察到MNTB体积或细胞数量的显著差异，表明PMCA 2不是MNTB神经元存活所需的。MNTB音调定位轴编码从内侧到外侧的高到低的声音频率。我们发现了一个细胞大小梯度沿着这条轴：外侧神经元胞体显着大于位于中间的胞体。这种尺寸梯度在+/dfw（2 J）中减小，而在dfw（2 J）/dfw（2 J）中不存在。缺乏声学驱动的输入表明，声音诱发的活动是维持细胞大小梯度所必需的。这一假设得到了证实，通过选择性消除听觉毛细胞的活动与毛细胞消除在Pou 4f 3 DTR小鼠或内耳河豚毒素（TTX）治疗。索马大小的变化是可逆的，并在TTX治疗7天内恢复，这表明梯度的调节依赖于突触活动，这些变化是可塑性的，而不是永久性的。新&值得注意的是，梯形体内侧核（MNTB）的神经元作为快速尖峰抑制性中间神经元内的听觉脑干。MNTB是地形组织，低频编码横向和高频中间。我们发现细胞大小沿着这个轴有梯度：外侧神经元比内侧神经元大。在缺乏质膜钙ATP酶2的耳聋小鼠中，这种梯度的缺乏表明了控制神经元索马体大小的活性依赖性、钙介导的机制。
The medial nucleus of the trapezoid body (MNTB) is an important source of inhibition during the computation of sound location. It transmits fast and precisely timed action potentials at high frequencies; this requires an efficient calcium clearance mechanism, in which plasma membrane calcium ATPase 2 (PMCA2) is a key component. Deafwaddler (dfw(2J)) mutant mice have a null mutation in PMCA2 causing deafness in homozygotes (dfw(2J)/dfw(2J)) and high-frequency hearing loss in heterozygotes (+/dfw(2J)). Despite the deafness phenotype, no significant differences in MNTB volume or cell number were observed in dfw2J homozygous mutants, suggesting that PMCA2 is not required for MNTB neuron survival. The MNTB tonotopic axis encodes high to low sound frequencies across the medial to lateral dimension. We discovered a cell size gradient along this axis: lateral neuronal somata are significantly larger than medially located somata. This size gradient is decreased in +/dfw(2J) and absent in dfw(2J)/dfw(2J). The lack of acoustically driven input suggests that sound-evoked activity is required for maintenance of the cell size gradient. This hypothesis was corroborated by selective elimination of auditory hair cell activity with either hair cell elimination in Pou4f3 DTR mice or inner ear tetrodotoxin (TTX) treatment. The change in soma size was reversible and recovered within 7 days of TTX treatment, suggesting that regulation of the gradient is dependent on synaptic activity and that these changes are plastic rather than permanent.NEW & NOTEWORTHY Neurons of the medial nucleus of the trapezoid body (MNTB) act as fast-spiking inhibitory interneurons within the auditory brain stem. The MNTB is topographically organized, with low sound frequencies encoded laterally and high frequencies medially. We discovered a cell size gradient along this axis: lateral neurons are larger than medial neurons. The absence of this gradient in deaf mice lacking plasma membrane calcium ATPase 2 suggests an activity-dependent, calcium-mediated mechanism that controls neuronal soma size.