The role of dendritic inputs in high-fidelity temporal processing of phase-coding neurons in the mammalian anteroventral cochlear nucleus

耳蜗前腹侧核的球状丛状细胞（SBC）以微秒级的精度编码听觉刺激的时间结构。为此，听觉脑干回路显示出显着程度的特定任务的专业化，特别是关于生物物理，细胞和突触硬件的超快和精确的听觉信息处理。然而，听觉脑干系统进化为在广泛的刺激条件下发挥最佳功能，这需要神经元功能的快速适应性。为此，也终止于AVCN的抑制性和调节性输入是潜在的候选者。在DFG优先计划1608的最后一个资助期，我们确定乙酰胆碱作为AVCN中时间编码神经元兴奋性的调节剂。将乙酰胆碱短暂地（毫秒至秒）以及张力性地（几分钟）应用于SBC使静息膜电位去极化。因此，它在两个不同的时间尺度上起作用。我们已经可以表明，快速去极化介导的离子型α-7 AChR。在本项目的第二个资金阶段，我们现在要详细说明乙酰胆碱在AVCN的行为的细胞机制。首先，我们想集中在紧张性调制反应的突触后效应。接下来，我们要系统地分析是否可以证实的调制效果的迹象突触前释放概率的内球的Held突触。最后，我们想研究胆碱能联合作用对SBC输出尖峰的时间敏锐度的影响。这些实验将在沙土鼠听觉脑干的急性切片制备中进行。将使用膜电位/电流的全细胞记录、药理学试剂的局部压力应用和轴突连接的电刺激的组合来解决我们的问题。除了体外实验之外，我们还希望应用一个数据约束的球形浓密细胞计算机模型，该模型是在第一阶段资助中创建的。这将使我们能够系统地研究调制输入和树突状兴奋的影响下，各种各样的模拟声音刺激paradigm.It的实验提出的目的是研究的机制，赋予刺激特异性的适应性超快速和精确的听觉脑干听觉系统的电路。

Spherical bushy cells (SBC) of the anteroventral cochlear nucleus code the temporal structure of the auditory stimulus with microsecond precision. For this the auditory brainstem circuitry shows a remarkable degree of task-specific specialization, especially regarding the biophysical, cellular and synaptic hardware for ultrafast and precise processing of auditory information. Auditory brainstem systems evolved however to optimally function over a wide range of stimulus conditions, which demands rapid adaptability of the neuronal function. For this, inhibitory and modulatory inputs that also terminate in the AVCN are potential candidates. In the last funding period of DFG priority program 1608 we identified acetylcholine as a modulator of the excitability of time-coding neurons in the AVCN. Application of acetylcholine to SBC transiently (milliseconds to seconds) and also tonically (several minutes) depolarizes the resting membrane potential. It thus acts on two different time scales. We could already show that the rapid depolarization is mediated by ionotropic alpha-7 AChR.In the second funding phase of this project we now want to elaborate on the cellular mechanisms by which acetylcholine acts in the AVCN. Initially we want to focus on postsynaptic effectors of the tonic modulatory response. Next, we want to systematically analyze whether indications of a modulatory effect on the presynaptic release probability of the endbulb of Held synapse can be confirmed. Finally, we want to study the effect the combined cholinergic influence has on the temporal acuity of the SBC output spiking.These experiments will be performed in acute slice preparations of the gerbil auditory brainstem. A combination of whole-cell recordings of membrane potentials/currents, local pressure application of pharmacological agents and electrical stimulation of axonal connections will be used to address our questions. In addition to the in-vitro experiments we want to apply a data-constrained computer model of the spherical bushy cells, which was created in funding phase 1. This will allow us to systematically study the effect of modulatory inputs and dendritic excitation under a wide variety of simulated sound-stimulus paradigms.It is the objective of the experiments proposed in this grant application to study a mechanism that imparts stimulus-specific adaptability to the ultra-fast and precise auditory brainstem circuitry of the auditory system.