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Role of L-type Ca2+-channels for development and function of the medial nucleus of the trapezoid body, an ultrafast relay center involved in sound localization

L 型 Ca2 通道对梯形体内侧核发育和功能的作用，梯形体内侧核是参与声音定位的超快中继中心

基本信息

批准号：
218321014
负责人：
Professor Dr. Eckhard Friauf
金额：
--
依托单位：
Fachgebiet Tierphysiologie
依托单位国家：
德国
项目类别：
Priority Programmes
财政年份：
2012
资助国家：
德国
起止时间：
2011-12-31 至 2015-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/218321014?language=en
关键词：
Role type Ca2+channels development

项目摘要

A hallmark of sound localization circuits in the mammalian auditory brainstem is ultrafast, secure and faithful neurotransmission. The medial nucleus of the trapezoid body (MNTB) takes an important part in these circuits as a temporally highly precise relay station. MNTB neurons invert excitatory input from the contralateral ear to inhibitory inputs to the ipsilateral lateral superior olive and the medial superior olive, two binaural centers, processing interaural level and time differences. The molecular mechanisms underpinning correct formation and function of these sound localization circuits are poorly understood. Own data identified a critical role of the L-type Ca2+-channels Cav1.2 and Cav1.3 in these processes. Here, we propose to unravel the precise function of these two channels in the MNTB. We will address both the functional consequences of auditory brainstem-specific loss of these two channels as well as their precise role for development and maturation of MNTB neurons. This will be done by applying state-of-the-art techniques on the genetic, molecular, cellular, and electrophysiological level up to the systems level. Taken all data together will provide important new insight into molecular mechanisms involved in the generation of unique specializations of the auditory system.

哺乳动物听觉脑干中声音定位回路的一个特点是超快、安全和可靠的神经传递。斜方体内侧核(MNTB)作为时间上高精度的中继站，在这些回路中起着重要作用。MNTB神经元翻转来自对侧耳的兴奋性输入到同侧外侧上橄榄和内侧上橄榄的抑制性输入，这是两个双耳中枢，处理耳间水平和时差。支持这些声音定位回路正确形成和功能的分子机制还知之甚少。OWN数据证实了L类钙通道Cav1.2和Cav1.3在这些过程中的关键作用。在这里，我们建议解开这两个渠道在MNTB中的确切功能。我们将讨论听觉脑干特异性丢失这两个通道的功能后果，以及它们在MNTB神经元发育和成熟中的确切作用。这将通过在遗传、分子、细胞和电生理水平上应用最先进的技术达到系统水平来实现。将所有数据放在一起，将为产生独特的听觉系统专门化的分子机制提供重要的新见解。