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

基本信息

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
项目类别：
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

项目摘要

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）：皮质法果 - 自上而下 - 从主听觉皮层（A1）到听觉脑干有力调节听觉处理的途径。一项重要的自上而下的途径是由皮质胶囊神经元介导的：A1中的层（L）5层神经元的子集，该神经元具有远距离轴突投射到下丘丘（IC）。皮质胶囊投影塑造了IC神经元的响应特性，并介导了声音定位学习。然而，先前对A1皮质法糖机制的生理研究并未具体靶向皮质骨化神经元。因此，基本的生理特性皮质胶囊神经元（例如其突触组织及其细胞特性）的含量在很大程度上未知。我们在该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皮质可胶状和L5皮质可质神经元的神经元-L5主要神经元投射到对侧皮层 - 差异化处理突触和声学输入。拟议的实验计划将提供有关皮质胶质和皮质可核糖L5神经元的突触，细胞和微电路特性的基本新信息。我们预计我们的发现将建立一个新的框架，以理解正常和疾病状态（例如耳鸣中的听觉过程）以及在病理声音和语音感知中的听觉处理中A1投影神经元在听觉过程中的作用。