Cellular Mechanisms of Auditory Information Processing

听觉信息处理的细胞机制

• 批准号: 7850212
• 负责人: Paul B Manis
• 金额: $ 11万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7850212
• 关键词: Ablation; Acoustic Nerve; Acoustics; Action Potentials; Adult; Affect; Analysis of Variance; Auditory; Biological Assay; Brain; Butyric Acids; Cells; Cochlear Implants; Cochlear nucleus; Complex; Computer Simulation; Data; Environment; Equilibrium; Generations; Glycine; Glycine Receptors; Hearing; High-Frequency Hearing Loss; Image; Inbred CBA Mice; Individual; Ion Channel; Kinetics; Literature; Mediating; Messenger RNA; Methods; Modeling; Mus; Neurons; Noise; Noise-Induced Hearing Loss; Organ; Pattern; Pharmacology; Play; Population; Probability; Process; Proteins; Residual state; Role; Sensory; Sensory Process; Slice; Sound Localization; Source; Speech Perception; Staging; Stimulus; Stream; Structure; Synapses; Techniques; Testing; Time; Training; auditory pathway; base; cell type; depression; dorsal cochlear nucleus; gamma-Aminobutyric Acid; hearing impairment; immunocytochemistry; information processing; insight; neural circuit; neuromechanism; postsynaptic; presynaptic; receptor; receptor expression; research study; response; sound; speech processing; stellate cell; synaptic function; synthetic enzyme

DESCRIPTION (provided by applicant): Central processing of the auditory environment begins with the generation of diverse, parallel, streams of information processing at the level of the first auditory center of the brain, the cochlear nucleus. These streams are created by populations of neurons with distinct patterns of synaptic inputs and projections. In order to accomplish their specific functions, the neurons in each stream utilize different cellular mechanisms, including ion channels that govern intrinsic excitability, and target-dependent synaptic inputs. Recent studies have shown that inhibition plays a much more important role in sculpting the responses of ventral cochlear nucleus (VCN) neurons to sound than previously appreciated. Inhibition can serve to enhance both the spectral and temporal processing of sound attributes that are important for sound identification and localization as well as speech processing. Our studies have revealed that the time course of inhibition, even from a single source, is different in the two principal cell types, the bushy and stellate cells. The first aim of this proposal is to clarify the functional synaptic organization of two local inhibitory synaptic circuits in the VCN. The second aim is to test the hypothesis that the synaptic currents on different cell types are mediated by different glycine receptor subunits. We will also investigate the presynaptic mechanisms that regulate the time course of release during sustained activity. The third aim is to incorporate this information into a detailed computational model, which will be used to explore the importance of different aspects of inhibition in temporal and spectral processing in the VCN. The fourth aim is to determine how the function of these inhibitory circuits is affected by hearing loss. All of these experiments will be performed in brain slices of adult mice. Overall, our studies will identify critical mechanisms in early auditory information processing, and determine how those mechanisms contribute to the analysis of complex sounds. We will then determine how these mechanisms are affected by hearing loss, which will provide insights for alternative stimulation strategies for the hard-of-hearing and for cochlear implant users. The neural mechanisms of sensory processing in the brain underlie our normal perceptual abilities, including the identification of sound sources and the ability to communicate through sound. These mechanisms are changed by damage to the sensory organs, and consequently, residual perceptual abilities are often adversely affected. In this project, we seek to understand the functional synaptic organization and the underlying mechanisms that contribute to hearing at early stages of the auditory pathway. We will also determine how these basic mechanisms are affected by hearing loss, and how hearing loss affects higher-order sensory processing in the brain. These experiments will ultimately generate insights for alternative stimulation strategies for the hard-of-hearing, and for cochlear implant users.

描述（由申请人提供）：听觉环境的中央处理开始于在大脑的第一听觉中心耳蜗核的水平上产生不同的、平行的信息处理流。这些流是由具有不同突触输入和投射模式的神经元群体产生的。为了完成它们的特定功能，每个流中的神经元利用不同的细胞机制，包括控制内在兴奋性的离子通道和靶依赖性突触输入。最近的研究表明，抑制在塑造耳蜗腹侧核（VCN）神经元对声音的反应中起着比以前认识到的更重要的作用。抑制可以用于增强声音属性的频谱和时间处理，这对于声音识别和定位以及语音处理是重要的。我们的研究表明，抑制的时间过程，即使是从一个单一的来源，是不同的两个主要的细胞类型，灌木和星状细胞。这个建议的第一个目的是澄清两个本地抑制性突触回路的VCN的功能性突触组织。第二个目的是检验不同类型细胞上的突触电流由不同甘氨酸受体亚基介导的假设。我们也将研究突触前机制，调节持续活动过程中释放的时间过程。第三个目的是将这些信息纳入一个详细的计算模型，这将被用来探索不同方面的抑制在VCN的时间和频谱处理的重要性。第四个目标是确定这些抑制回路的功能如何受到听力损失的影响。所有这些实验都将在成年小鼠的脑切片中进行。总的来说，我们的研究将确定早期听觉信息处理的关键机制，并确定这些机制如何有助于复杂声音的分析。然后，我们将确定这些机制如何受到听力损失的影响，这将为听力困难和人工耳蜗植入用户提供替代刺激策略的见解。大脑中感觉处理的神经机制是我们正常感知能力的基础，包括识别声源和通过声音进行交流的能力。这些机制因感觉器官受损而改变，因此，残余的感知能力往往受到不利影响。在这个项目中，我们试图了解功能性突触组织和潜在的机制，有助于在听觉通路的早期阶段的听力。我们还将确定这些基本机制如何受到听力损失的影响，以及听力损失如何影响大脑中的高阶感觉处理。这些实验最终将为听力障碍者和人工耳蜗植入者提供替代刺激策略的见解。