Synaptic mechanisms in the auditory system (Administrative Supplement)

听觉系统中的突触机制（行政补充）

• 批准号: 9189038
• 负责人: LAURENCE O TRUSSELL
• 金额: $ 3.56万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-05 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9189038
• 关键词: Acetylcholine; Acoustic Nerve; Administrative Supplement; Amplifiers; Area; Auditory; Auditory system; Back; Biological Assay; Biophysical Process; Brush Cell; Cells; Chronic; Clinical; Communication; Cytoplasmic Granules; Data; Dimensions; Ear; Electrical Synapse; Electrophysiology (science); Elements; Feedback; Fiber; Fusiform Cell; GABA Receptor; Goals; Golgi Apparatus; Head; Health; Hyperactive behavior; Interneurons; Lateral; Maintenance; Mediating; Modality; Mus; Neuromodulator; Neurons; Norepinephrine; Optics; Play; Process; Prosthesis; Role; Sensory; Signal Transduction; Source; Staging; Structure of molecular layer of cerebellar cortex; Synapses; Synaptic plasticity; Testing; Tinnitus; auditory pathway; biophysical properties; carbon fiber; cell type; cholinergic; design; dorsal cochlear nucleus; excitatory neuron; feeding; fluorophore; granule cell; inhibitory neuron; insight; mossy fiber; multisensory; neural circuit; neuroregulation; noradrenergic; novel; receptor; research study; signal processing; sound; stellate cell; transmission process; voltage

DESCRIPTION (provided by applicant): Our long-term goal is to understand how neural circuits support auditory processing. Here, we will explore dynamic aspects of synaptic communication, their neuromodulation and plasticity, in the molecular layer and granule cell regions of the dorsal cochlear nucleus (DCN). The results of this study will reveal novel aspects of DCN circuit elements, information which will add new dimensions to the current picture of auditory and multisensory processing. The DCN functions in sound source localization and the integration of a variety of non-auditory signals, potentially for head/ear orientation or cancelatin of self-generated sound. It is also believed that the DCN plays a role in the maintenance of tinnitus, a widespread and disturbingly chronic clinical condition. The DCN is unique in the lower auditory pathway for showing robust synaptic plasticity - this is plasticity not of the auditory nerve input but rather of multisensory input, highlighting the important role that latter must have in DCN function. This proposal examines two sequential stages of multisensory processing: first in auditory granule cells and then in the DCN molecular layer. All multisensory information enters the DCN through mossy fibers which terminate in seven sub regions of granule cells. Yet, the different roles of these granule regions and what distinct forms of processing occur in each are unknown. We will therefore clarify how granule cells transform signals in order to understand the significance of computations later in the circuit. In the molecular layer, parallel fibers of granule cells terminate onto fusiform principal cells and two interneurons, the cartwheel cell and the superficial stellate cell (SSC). Here we will explore an unexpected function for the SSCs, that they mediate feedback signaling from the principal cells that facilitates activity withi the molecular layer. Lastly, we will determine how processing in granule areas and the molecular layer is controlled by the potent neuromodulators. We will use electrophysiological and optical approaches, and generate new mouse lines in which fluorophores or channelrhodopsin (ChR2) are expressed in specific DCN cell types.

描述（由申请人提供）：我们的长期目标是了解神经电路如何支持听觉处理。在这里，我们将探索突触通信的动态方面，它们的神经调节和可塑性，在背侧耳蜗核的分子层和颗粒细胞区域（DCN）。这项研究的结果将揭示DCN电路元素的新方面，信息将为当前听觉和多感官处理的图片增加新的维度。 DCN在声源本地化和各种非审计信号的集成中起作用，有可能用于头/耳朵方向或自我生成声音的取消。还认为，DCN在维持耳鸣中起作用，这是一种普遍且令人不安的慢性临床状况。 DCN在较低的听觉途径中是独一无二的，可以显示出鲁棒的突触可塑性 - 这不是听觉神经输入的可塑性，而是多感官输入，强调了后者必须具有的重要作用 在DCN功能中。该建议检查了多感觉处理的两个顺序阶段：在听觉颗粒细胞中，然后在DCN分子层中。所有多感官信息均通过在颗粒细胞的七个子区域终止的苔藓纤维进入DCN。然而，这些颗粒区域的不同作用以及在每种颗粒中发生的不同形式的处理形式是未知的。因此，我们将阐明颗粒细胞如何变形信号，以了解后期计算的重要性。在分子层中，颗粒细胞的平行纤维终止于梭形主细胞和两个中间神经元，Cartwheel 细胞和浅表星细胞（SSC）。在这里，我们将探索SSC的意外功能，它们介导了用分子层促进活性的主要细胞中的反馈信号传导。最后，我们将确定颗粒区域和分子层的加工如何由有效的神经调节剂控制。我们将使用电生理和光学方法，并生成新的小鼠系，其中荧光团或通道旋转蛋白（CHR2）在特定的DCN细胞类型中表达。