Analysis of the cellular mechanisms promoting fast information transfer at a large synapse in the ventral nucleus of the lateral lemniscus

这一建议旨在阐明与语音识别有关的超快听觉回路中的突触生理学和信息传递的生物物理学。外侧丘脑腹侧核(VNLL)在宽带刺激下调节为高强度，被认为是下丘神经元到达重要声音信息的启动。我们的研究试图理解这个电路是如何在VNLL水平上产生从激发到抑制的时间精确反转的。我们使用蒙古沙土鼠的急性脑片，从视觉上识别的VNLL突触前和突触后隔区进行单细胞和双全细胞记录，并配对进行传出纤维刺激。我们将确定突触前钙通道的性质和类型、递质释放以及突触强度对突触后动作电位产生的影响。突触后，我们着重阐明电压门控性钾通道的分子同一性及其与兴奋性突触电流的相互作用。这些数据将与众所周知的梯形体内内侧核内固定突触花瓣的记录进行比较。从这种对突触信息传递的比较生物物理分析中，我们试图理解由大型听觉突触产生的维持时间精度的一般机制。

This proposal aims to elucidate the synaptic physiology and the biophysics of information transfer in an ultrafast auditory circuit that is implicated in speech recognition. The ventral nucleus of the lateral lemniscus (VNLL) is tuned to high intensity onsets of broadband stimuli and is thought to prime neurons in the inferior colliculus for the arrival of important sound information. Our investigations try to understand how this circuitry generates a temporally precise inversion from excitation to inhibition on the level of VNLL. We use acute brain slices of Mongolian gerbils to perform single and dual whole-cell recordings from visually identified pre- and postsynaptic compartments in the VNLL, paired with efferent fiber stimulations. We will determine the properties and types of presynaptic calcium channels, transmitter release and the implication of the synaptic strength on the postsynaptic action potentials generation. Postsynaptically we focus on elucidating the molecular identity of voltage gated potassium channels and their interplay with excitatory synaptic currents. These data will be compared to recordings at the well known calyx of Held synapse in the medial nucleus of the trapezoid body. From this comparative, biophysical analysis of the synaptic information transfer we seek to understand the general mechanisms underlying the maintenance of temporal precision produced by large auditory synapses.