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

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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.