Cellular Mechanisms Underlying Corticocollicular Modulation in the Auditory Syste

听觉系统中皮质小丘调节的细胞机制

• 批准号: 8803418
• 负责人: Gordon M Shepherd
• 金额: $ 32.72万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8803418
• 关键词: Acoustics; Address; Affect; Auditory; Auditory area; Auditory system; Axon; Behavioral; Brain Stem; Cells; Contralateral; Coupled; Development; Disease; Electrophysiology (science); Foundations; Frequencies; Functional disorder; Future; Goals; Health; Hearing; Inferior Colliculus; Interneurons; Knowledge; Lead; Learning; Medial geniculate body; Mediating; Mission; Modeling; Neurons; Output; Pathology; Pathway interactions; Physiological; Physiology; Process; Property; Public Health; Research; Role; Shapes; Signal Transduction; Sound Localization; Source; Speech Perception; Structure; Synapses; Testing; Thalamic structure; Tinnitus; United States National Institutes of Health; base; cell type; cellular targeting; clinically relevant; data modeling; design; disability; hearing impairment; hippocampal pyramidal neuron; improved; in vivo; nervous system disorder; neural circuit; novel; novel therapeutic intervention; optogenetics; prevent; programs; response; tool

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.

描述（由申请人提供）：皮质 - 自上而下 - 从初级听觉皮层 (A1) 到听觉脑干的通路强有力地调节听觉处理。一个重要的自上而下的通路是由皮质丘神经元介导的：A1 中第 5 层锥体神经元的子集，具有向下丘 (IC) 的长距离轴突投射。皮质丘状投射塑造 IC 神经元的反应特性，并介导声音定位学习。然而，之前对 A1 离皮质机制的生理学研究并没有专门针对皮质皮质神经元。因此，基本生理特性 皮质球神经元的功能，例如它们的突触组织和细胞特性，在很大程度上仍然未知。我们在这项提案中的主要目标是确定细胞特异性的细胞和突触机制，这些机制决定了 L5 皮质皮质神经元和 L5 皮质胼胝体神经元（投射到对侧皮质的 L5 主要神经元）如何差异化处理突触 和声音输入。拟议的实验计划将提供有关皮质丘状和皮质胼胝体 L5 神经元的突触、细胞和微电路特性的基本新信息。我们期望我们的研究结果将建立一个新的框架，用于理解 A1 投射神经元在正常和疾病状态下（例如耳鸣和病理性声音和言语感知）听觉处理的自上而下的皮质小球调节中的作用。