The influence of descending cholinergic connections on information processing in the initial stages of the central auditory pathway

乙酰胆碱可调节耳蜗腹侧核主神经元的兴奋性。这种神经调节在听觉信息处理中的作用尚不清楚。因此，我们希望在麻醉的蒙古沙鼠（Meriones unguiculatus）的腹侧耳蜗核中离子传导地应用胆碱能激动剂和拮抗剂，同时记录主要神经元的声音驱动反应。进入耳蜗腹侧核的胆碱能轴突的一部分来自脑桥前部被盖的神经元，这些神经元对声音刺激有反应。在声音加工过程中，下行胆碱能与皮层下听觉区连接的刺激调谐和功能作用尚不清楚。我们想要记录脑桥前部被盖的神经元，并探索最能驱动这些神经元的声音刺激条件。此外，我们希望通过注射轴突示踪物质和随后的组织学分析来绘制它们与蒙古沙鼠皮层下感觉区域的连通性。最后，我们想直接测量下行连接对腹侧耳蜗核声音处理的影响。为此，我们将电激活脑桥前部的神经元，同时记录腹侧耳蜗核主要神经元的声音驱动反应。本项目提案中的实验将有助于理解和量化下行神经调节对皮层下感觉通路中信息处理的影响。

Excitability of principal neurons in the ventral cochlear nucleus is modulated by acetylcholine. The role of this neuromodulation in auditory information processing is not well understood. We thus want to iontophoretically apply cholinergic agonists and antagonists in the ventral cochlear nucleus of the anesthetized mongolian gerbil (Meriones unguiculatus) while simultaneously recording the sound driven responses of principal neurons. A subset of cholinergic axons entering the ventral cochlear nucleus arises from neurons in the pontomesencephalic tegmentum, which are known to be responsive to sound stimulation. The stimulus tuning and the functional role of the descending cholinergic connectivity with subcortical auditory areas during sound processing is unknown. We want to record from neurons in the pontomesencephalic tegmentum and explore the sound stimulus conditions that best drive these neurons. Furthermore we want to map their connectivity with subcortical sensory areas in the mongolian gerbil by injection of axonal tracer substances and subsequent histological analysis. Finally, we want to directly measure the effect of descending connections on sound processing in the ventral cochlear nucleus. For this we will electrically activate neurons in the pontomesencephalic while simultaneously recording sound-driven responses from principal neurons in the ventral cochlear nucleus. The experiments in this project proposal will help to understand and quantify the effects of descending neuromodulation on information processing in a subcortical sensory pathway.