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回路如何支持听觉处理。在这里，我们将探索耳蜗背核 (DCN) 分子层和颗粒细胞区域中突触通讯的动态方面、神经调节和可塑性。这项研究的结果将揭示 DCN 电路元件的新颖方面，这些信息将为当前的听觉和多感官处理图景增添新的维度。 DCN 的功能在于声源定位和各种非听觉信号的集成，可能用于头/耳定向或消除自生声音。人们还认为，DCN 在耳鸣的维持中发挥着重要作用，耳鸣是一种广泛存在且令人不安的慢性临床病症。 DCN 在下听觉通路中是独一无二的，它显示出强大的突触可塑性 - 这不是听觉神经输入的可塑性，而是多感觉输入的可塑性，突出了后者必须具有的重要作用 在 DCN 功能中。该提案研究了多感觉处理的两个连续阶段：首先在听觉颗粒细胞中，然后在 DCN 分子层中。所有多感觉信息通过苔藓纤维进入 DCN，苔藓纤维终止于颗粒细胞的七个子区域。然而，这些颗粒区域的不同作用以及每个区域发生的不同处理形式尚不清楚。因此，我们将阐明颗粒细胞如何转换信号，以便理解电路中稍后计算的重要性。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（侧手翻） 细胞和浅层星状细胞（SSC）。在这里，我们将探索 SSC 的一个意想不到的功能，即它们介导来自主细胞的反馈信号，从而促进分子层内的活动。最后，我们将确定有效的神经调节剂如何控制颗粒区域和分子层的加工。我们将使用电生理学和光学方法，并产生新的小鼠系，其中荧光团或视紫红质通道蛋白 (ChR2) 在特定 DCN 细胞类型中表达。