Cellular Mechanisms of Auditory Information Processing

听觉信息处理的细胞机制

基本信息

批准号：
7201637
负责人：
Paul B Manis
金额：
$ 30.42万
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 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7201637
关键词：
AMPA Receptors Acids Acoustic Nerve Acoustic Stimulation Acoustics Action Potentials Adult Affect Animals Anterior Area Atrial Natriuretic Factor Auditory Auditory system Brain Butyric Acid Butyric Acids Cadherins Cells Cholinergic Agents Cholinergic Receptors Chromosome Pairing Chronic Cochlear nucleus Code Communication Computer Simulation Computer information processing Condition Cues Effectiveness Environment Exhibits Face Fire - disasters GABA-A Receptor GluR2 subunit AMPA receptor Glycine Goals Hair Cells Hearing Human In Vitro Inhibitory Synapse Interneurons Ion Channel Kinetics Lateral Light Link Measures Mental Depression Methods Modeling Mus Mutate Mutation N-Methylaspartate Neurons Noise Octopus Operative Surgical Procedures Pathway interactions Pattern Peripheral Play Potassium Potassium Channel Probability Process Property Range Rate Rattus Research Personnel Rest Retinal Degeneration Role Simulate Slice Sound Localization Source Speech Speech Perception Staging Stimulus Structure Synapses Synaptic Transmission Syndrome System Testing Time Training Work auditory pathway cell type cholinergic cholinergic neuron concept deafness design dorsal cochlear nucleus experience ganglion cell hearing impairment human CDH23 protein improved in vivo insight mouse model nerve supply neurotransmitter release postsynaptic presynaptic programs receptor receptor expression receptor function relating to nervous system research study response sensory system sound stellate cell synaptic depression tool

项目摘要

DESCRIPTION (provided by applicant): The central auditory system exhibits a remarkable ability to extract information from a limited representation of the acoustic environment provided by the auditory nerve. Auditory information is first analyzed in the cochlear nucleus, where auditory nerve spike trains are transformed to create a set of parallel ascending pathways that emphasize different aspects of the acoustic environment. These transformations play essential roles in determining the source of a sound and in auditory communication. Recent studies have shown that the cellular mechanisms underlying neural integration in the cochlear nucleus are altered by hearing loss. In this proposal, we will investigate the integrative mechanisms of anterior ventral cochlear nucleus (AVCN) bushy neurons in normal animals, and in animals experiencing chronic hearing loss. We propose 3 aims. In the first aim, we will test explicit hypotheses about the subthreshold integrative mechanisms of AVCN bushy neurons using in vitro methods and dynamic clamp to apply realistic patterns of synaptic conductance changes that represent the activity expected with acoustic stimulation. We will test hypotheses about how the potassium conductances contribute to integration of synaptic inputs. We will also evaluate how tonotopic gradients of ion channel expression affect integration. In the second aim, we will test the hypothesis that the two primary sources of inhibition to bushy cells utilize synapses with different release properties and temporal dynamics. We will test whether inhibition is necessary to improve temporal fidelity of timing information, and whether inhibition helps to provide a sparse code to more central synapses. We will also document the organization of the functional circuitry within the AVCN through paired recordings between inhibitory interneurons and principal neurons. In the third aim, we will examine synaptic transmission at both excitatory and inhibitory synaptic inputs in a mouse model of hearing loss. We will test the hypothesis that hearing loss causes the postsynaptic receptors to return to an immature state. We will characterize the synaptic conductances and dynamics of neurons experiencing hearing loss. Finally, we will also investigate the more speculative hypothesis that there are compensatory changes in nicotinic cholinergic receptor function in the AVCN, since there is evidence that innervation of the cochlear nucleus by cholinergic afferents may be increased after profound hearing loss. These experiments will help us understand how information is processed in the central auditory system under normal hearing conditions, and will shed light on functional and cellular changes in central processing that occur in hearing loss and deafness. Understanding these dynamic changes is an essential step toward developing compensatory or corrective strategies to restore hearing and optimize auditory communication in the face of hair cell and ganglion cell loss

描述（由申请人提供）：中枢听觉系统表现出从听觉神经提供的声学环境的有限表示中提取信息的非凡能力。听觉信息首先在耳蜗核中进行分析，其中听觉神经尖峰序列被转换以创建一组平行的上升路径，这些路径强调声学环境的不同方面。这些转换在确定声音来源和听觉交流中发挥着重要作用。最近的研究表明，听力损失会改变耳蜗核中神经整合的细胞机制。在本提案中，我们将研究正常动物和慢性听力损失动物中前腹侧耳蜗核（AVCN）浓密神经元的整合机制。我们提出 3 个目标。第一个目标是，我们将使用体外方法和动态钳来测试关于 AVCN 浓密神经元阈下整合机制的明确假设，以应用代表声刺激预期活动的突触电导变化的现实模式。我们将测试有关钾电导如何促进突触输入整合的假设。我们还将评估离子通道表达的音调梯度如何影响积分。在第二个目标中，我们将测试以下假设：对浓密细胞的抑制的两个主要来源利用具有不同释放特性和时间动态的突触。我们将测试抑制是否对于提高定时信息的时间保真度是必要的，以及抑制是否有助于向更中心的突触提供稀疏代码。我们还将通过抑制性中间神经元和主要神经元之间的配对记录来记录 AVCN 内功能电路的组织。在第三个目标中，我们将检查听力损失小鼠模型中兴奋性和抑制性突触输入的突触传递。我们将检验听力损失导致突触后受体恢复到不成熟状态的假设。我们将描述经历听力损失的神经元的突触电导和动力学特征。最后，我们还将研究更具推测性的假设，即 AVCN 中的烟碱胆碱能受体功能存在代偿性变化，因为有证据表明，在严重听力损失后，胆碱能传入对耳蜗核的神经支配可能会增加。这些实验将帮助我们了解正常听力条件下中枢听觉系统如何处理信息，并将揭示听力损失和耳聋时中枢处理功能和细胞的变化。了解这些动态变化是制定补偿或纠正策略的重要一步，以在毛细胞和神经节细胞损失的情况下恢复听力并优化听觉交流