Cellular Mechanisms Underlying Corticocollicular Modulation in the Auditory Syste

描述(由申请人提供)：从初级听觉皮质(A1)到听觉脑干的皮质分离-自上而下-通路强烈地调节听觉处理。一个重要的自上而下通路是由皮质小丘神经元介导的：A1区具有长距离轴突投射到下丘(IC)的5层锥体神经元的一个子集(L)。皮质小脑投射塑造了IC神经元的反应特性，并介导了声音定位学习。然而，以前对A1皮质分离机制的生理学研究并没有专门针对皮质小脑神经元。因此，基本的生理特性 皮质小脑神经元的结构，例如它们的突触组织和它们的细胞特性，在很大程度上仍然不清楚。我们在这个提案中的主要目标是确定细胞特有的细胞和突触机制，这些机制决定了L5皮质和L5皮质--投射到对侧皮质的L5主要神经元--如何不同地处理突触。 和声学输入。拟议的实验计划将提供有关皮质小脑和皮质穹隆L5神经元的突触、细胞和微电路特性的基本新信息。我们希望我们的发现将建立一个新的框架，以了解A1投射神经元在正常和疾病状态下，如耳鸣和病理性声音和语音感知中自上而下调节听觉处理的皮质交感神经调节中的作用。

DESCRIPTION (provided by applicant): Corticofugal - top-down - pathways from primary auditory cortex (A1) to the auditory brainstem powerfully modulate auditory processing. One important top-down pathway is mediated by corticocollicular neurons: a subset of layer (L) 5 pyramidal neurons in A1 with long-range axonal projections to the inferior colliculus (IC). The corticocollicular projection shapes the response properties of IC neurons, and mediates sound localization learning. However, previous physiological studies of A1 corticofugal mechanisms have not specifically targeted corticocollicular neurons. Therefore, basic physiological properties of corticocollicular neurons, such as their synaptic organization and their cellular properties, remain largely unknown. Our major goal in this proposal is to identify the cell-specific cellular and synaptic mechanisms that determine how L5 corticocollicular and L5 corticocallosal neurons - L5 principal neurons projecting to contralateral cortex - differentially process synaptic and acoustic input. The proposed experimental program will provide fundamental new information about the synaptic, cellular, and microcircuit properties of corticocollicular and corticocallosal L5 neurons. We expect that our findings will establish a new framework for understanding the roles of A1 projection neurons in top-down corticocollicular modulation of auditory processing in normal and disease states, such as in tinnitus and in pathological sound and speech perception.