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）到听觉脑干的自上而下的皮质通路有力地调节听觉加工。一个重要的自上而下的通路是由皮质丘神经元介导的：A1层(L) 5锥体神经元的一个子集具有远程轴突投射到下丘（IC）。皮质-丘投影形成IC神经元的反应特性，并介导声音定位学习。然而，先前关于A1皮质机制的生理学研究并没有专门针对皮质丘神经元。因此，基本生理特性