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特点是超快、安全、可靠的神经传递。梯形体内侧核在这些电路中起着重要的作用，是一个时间上高精度的中继站。MNTB神经元将来自对侧耳的兴奋性输入倒转到同侧侧橄榄上外侧和内侧橄榄上两个双耳中枢的抑制性输入，处理耳间水平和时间差异。支持这些声音定位电路正确形成和功能的分子机制尚不清楚。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，我们提出揭示这两个通道在MNTB中的确切功能。我们将讨论这两个通道的听觉脑干特异性损失的功能后果，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直至系统水平来完成。把所有的数据放在一起，将提供重要的新见解的分子机制参与产生独特的专业化的听觉系统。

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.