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）：从初级听觉皮层（A1）到听觉脑干的离皮质-自上而下-通路有力地调节听觉处理。一个重要的自上而下的途径是由皮质丘神经元介导的：A1中的第5层（L）锥体神经元的子集，具有到下丘（IC）的长距离轴突投射。皮质丘投射塑造了IC神经元的反应特性，并介导了声音定位学习。然而，以前的生理研究A1离皮质机制没有专门针对皮质丘神经元。因此，基本的生理特性 皮质丘神经元的突触组织和细胞特性等仍不清楚。我们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皮质丘和L5皮质胼胝体神经元--投射到对侧皮质的L5主要神经元--如何差异地处理突触。 和声音输入。拟议的实验计划将提供有关皮质丘和皮质胼胝体L5神经元的突触，细胞和微电路特性的基本新信息。我们希望我们的研究结果将建立一个新的框架，了解A1投射神经元在自上而下的皮质丘调制的听觉处理在正常和疾病状态下，如耳鸣和病理性的声音和语音感知的作用。