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

乙酰胆碱对耳蜗腹侧核主神经元兴奋性的调节。这种神经调节在听觉信息处理中的作用还不清楚。因此，我们希望应用胆碱能激动剂和拮抗剂在麻醉的蒙古沙鼠（长爪沙鼠）的腹侧耳蜗核，同时记录的声音驱动的主要神经元的反应。进入耳蜗腹侧核的胆碱能轴突的一个子集来自桥中脑被盖中的神经元，已知其对声音刺激有反应。在声音处理过程中，下行胆碱能连接与皮层下听觉区的刺激调谐和功能作用是未知的。我们想记录下桥中脑被盖的神经元，并探索最能驱动这些神经元的声音刺激条件。此外，我们想通过注射轴突示踪物质和随后的组织学分析来绘制蒙古沙鼠皮层下感觉区与它们的连接。最后，我们想直接测量耳蜗腹侧核下行连接对声音处理的影响。为此，我们将电激活脑桥中脑的神经元，同时记录耳蜗腹侧核中主要神经元的声音驱动反应。本计画中的实验将有助于了解和量化皮质下感觉通路中下行神经调变对信息处理的影响。

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.