Cellular Mechanisms of Auditory Information Processing

听觉信息处理的细胞机制

基本信息

批准号：
8837092
负责人：
Paul B Manis
金额：
$ 37.35万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-09-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8837092
关键词：
Acoustic Nerve Acoustics Address Affect Auditory Brain Cells Cochlear Implants Cochlear nucleus Computer Simulation Cues Data Detection Dorsal Environment Equilibrium Frequencies Glutamate Decarboxylase Glycine Goals Hearing Hearing Aids High-Frequency Hearing Loss Interneurons Left Measures Modeling Mus Neurons Noise Noise-Induced Hearing Loss Organ Outcomes Research Output Pathway interactions Pattern Peripheral Population Population Projection Process Relative (related person)Research Residual state Role Sensory Sensory Process Shapes Signal Transduction Slice Source Staging Stereotyping Stimulus Structure Synapses Techniques Testing Time Tissues Training Vision Work auditory pathway cell type cellular targeting dorsal cochlear nucleus hearing impairment in vivo in vivo Model information processing insight network architecture network models neural circuit neuromechanism optogenetics patch clamp programs public health relevance receptor expression reconstruction research study response restoration sound stellate cell synaptic function

项目摘要

DESCRIPTION (provided by applicant): Neurons and neural circuits in the cochlear nuclei are on the front line of auditory information processing. The CN receives a stereotyped representation of sound in the form of spike trains from the auditory nerve (AN), and produces highly modified parallel representations that drive the ascending auditory pathways. Traditionally, the cochlear nuclei are viewed as consisting of three major regions containing distinct populations of projection neurons that each emphasize different aspects of information about the acoustic environment in a parallel, but largely independent, fashion. However, coordinated spiking between output pathways can aid in the reconstruction of auditory objects and the detection of signals in noise by providing temporal cues that contribute to integration in higher auditory neurons. Our overarching hypothesis is that the relative spike timing between these pathways is coordinated not only by features in the acoustic stimulus, but importantly by shared local excitatory and inhibitory circuits, implying that the pathways are not independent. Coordinated activity may aid in the reconstruction of auditory objects and the detection of signals in noise by providing temporal coherence of activity across cells that can be integrated when these pathways converge onto higher auditory neurons. Yet, how the local circuits contribute to processing and their connectivity with other cells in the cochlear nuclei are only partially understood. In this proposal, we address how the output pathways of the cochlear nuclei can be coordinated through local circuits. The first stage of the work takes place in the context of normal hearing, and examines hypotheses about the functional synaptic connectivity of three cell types in the cochlear nuclei with the principal neurons and with each other, using optogenetic techniques and targeted patch clamp recording in brain slices form mice. The second stage incorporates the spatial structure of these circuits and the temporal dynamics of their synapses into a network model to evaluate how the activity between and within the output pathways is structured by the local circuits. We will then test predictions from the model with in vivo single unit studies. The finals stage considers the effects of a high-frequency noise-induced hearing loss on the functional organization of the CN circuit to determine how excitatory and inhibitory balance is altered. The rationale of the proposed research is that the successful restoration of function with cochlear implants or hearing aids depends on the ability to optimally engage the functional network architecture of the cochlear nucleus, which in turn requires an understanding of how information is integrated in the cochlear nuclei and how the output activity is coordinated by the local networks.

描述（由申请人提供）：耳蜗核中的神经元和神经回路处于听觉信息处理的最前线。 CN 从听觉神经 (AN) 接收尖峰序列形式的声音刻板表征，并产生高度修改的并行表征，驱动上行听觉通路。传统上，耳蜗核被视为由三个主要区域组成，其中包含不同的投射神经元群，每个区域以平行但基本上独立的方式强调有关声学环境的信息的不同方面。然而，输出通路之间的协调尖峰可以通过提供有助于高级听觉神经元整合的时间线索来帮助听觉对象的重建和噪声中信号的检测。我们的总体假设是，这些通路之间的相对尖峰时间不仅通过声刺激的特征来协调，而且重要的是通过共享的局部兴奋和抑制电路来协调，这意味着这些通路不是独立的。协调的活动可以通过提供跨细胞活动的时间一致性来帮助听觉对象的重建和噪声中信号的检测，当这些通路汇聚到更高的听觉神经元时，这些活动可以被整合。然而，局部电路如何促进处理以及它们与耳蜗核中其他细胞的连接仅得到部分了解。在该提案中，我们讨论了如何通过局部电路协调耳蜗核团的输出路径。该工作的第一阶段在正常听力的背景下进行，并使用光遗传学技术和大脑中的靶向膜片钳记录，检查有关耳蜗核中三种细胞类型与主要神经元以及彼此之间功能性突触连接的假设切片形成小鼠。第二阶段将这些电路的空间结构及其突触的时间动态纳入网络模型中，以评估输出路径之间和内部的活动如何由局部电路构建。然后，我们将通过体内单个单元研究来测试模型的预测。决赛阶段考虑高频噪声引起的听力损失对中枢神经回路功能组织的影响，以确定兴奋性和抑制性平衡如何改变。该研究的基本原理是，人工耳蜗或助听器功能的成功恢复取决于最佳地参与耳蜗核功能网络架构的能力，而这反过来又需要了解信息如何整合到耳蜗核中以及本地网络如何协调输出活动。