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

哺乳动物听觉脑干中声音定位回路的一个标志是超快、安全和忠实的神经传递。斜方体内侧核（MNTB）作为一个时间上高度精确的中继站，在这些回路中起着重要的作用。MNTB神经元将对侧耳的兴奋性输入转化为同侧外侧上级橄榄和内侧上级橄榄的抑制性输入，这两个双耳中心处理耳间水平和时间差异。这些声音定位电路正确形成和功能的分子机制还知之甚少。自己的数据确定了L型Ca2+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的确切功能。我们将解决这两个通道的听觉脑干特异性损失的功能后果，以及它们对MNTB神经元发育和成熟的确切作用。这将通过在遗传、分子、细胞和电生理水平直至系统水平上应用最先进的技术来完成。将所有数据放在一起将为研究听觉系统独特专业化产生所涉及的分子机制提供重要的新见解。

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.