PHYSIOLOGY OF DORSAL COCHLEAR NUCLEUS MOLECULAR LAYER

耳蜗背核分子层的生理学

• 批准号: 2683902
• 负责人: Paul B Manis
• 金额: $ 24.59万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2683902
• 关键词: auditory nuclei; auditory pathways; auditory stimulus; calcium flux; calcium indicator; dendrites; fluorescent dye /probe; granule cell; histology; intercellular connection; interneurons; laboratory rat; membrane potentials; mossy fiber; neural conduction; neural information processing; neural plasticity; neurophysiology; single cell analysis; synapses; tissue /cell culture

DESCRIPTION (Adapted from the Investigator's Abstract): The dorsal cochlear nucleus is a relatively complex neural region whose function may be to provide rapid and early processing of complex acoustic stimuli, and to form associations between auditory and non-auditory events. The proposed experiments investigate the cellular mechanisms of information processing in the circuitry of the molecular layer of this nucleus. This circuitry consists of an obligatory set of interneurons, the granule cells, which receive input from diverse mossy fiber afferents and in turn form excitatory parallel fibers that innervate two major targets: a set of inhibitory neurons, the cartwheel cells, and the principal projection neurons of the nucleus, the pyramidal cells. The aims of this proposal trace the transformations that take place at 3 key points in this circuit: at the mossy-fiber granule cell synapse, at the synapses between parallel fibers and their postsynaptic targets, and in the dendrites of cells postsynaptic to the parallel fibers. In the first aim, synaptic integration at the mossy-fiber granule cell synapse will be examined. They hypothesize that granule cells act as coincidence detectors, and require near-simultaneous activation of at least two mossy fiber inputs in order to discharge action potentials. They will also examine the intrinsic discharge of the granule cells, and the role of Golgi-cell inhibition in regulating the transmission through these cells. In the second aim, we hypothesize that the parallel fiber synapses on cartwheel cells and pyramidal cells are a site of synaptic plasticity, and we will investigate the specific requirements for calcium elevation, activation of neurotransmitter receptors, and activation of protein kinase C that may underlie long term changes in synaptic function. In the third aim, we will investigate the way in which postsynaptic potentials are integrated in the dendritic trees of pyramidal and cartwheel cells. The investigators hypothesize that the different patterns of dendritic branching in these cells, and the presence of active voltadependent channels in their dendrites, will be associated with different characteristics of synaptic integration of activity from their shared source, the parallel fibers. They will determine the sites and types of conductances present in the dendritic trees using optical imaging techniques, and will compare features of synaptic integration in the two cell types using focal activation of one and two discrete clusters of parallel fibers inputs to the dendritic tree under different conditions. All of these experiments utilize tight-seal recording of visualized and identified neurons in brain slices from young rats, and some experiments also utilize time domain imaging of single cells loaded with fluorescent ion-sensitive dyes. The results of these experiments will help us to understand key cellular mechanisms involved in neural integration of information in the inputs that are relayed into the cochlear nucleus through the granule cell system. The results derived from these studies will have an impact on our understanding of information processing in the dorsal cochlear nucleus and its dynamic characteristics, and may suggest new functions for this primary auditory center. These studies may also lead to new knowledge about the general rules of information processing in the dendrites of neurons throughout the brain.

描述（改编自研究者摘要）：背侧 耳蜗核是一个相对复杂的神经区域， 可以提供对复杂声学信号的快速和早期处理， 刺激，并形成听觉和非听觉之间的联系 事件拟议的实验研究的细胞机制， 这种分子层的电路中的信息处理 原子核这个回路由一组必不可少的中间神经元组成， 颗粒细胞接受来自不同苔藓纤维的信息 传入神经，反过来又形成兴奋性平行纤维， 主要靶点：一组抑制性神经元，侧手翻细胞，以及 主要投射神经元的核，锥体细胞。的 该提案的目的是跟踪发生在3个关键的转变， 在这个回路中的点：在苔藓纤维颗粒细胞突触，在 突触之间的平行纤维和他们的突触后目标，并在 突触后细胞的树突与平行纤维相连。 在 第一个目标，在苔藓纤维颗粒细胞突触处的突触整合 将被审查。 他们假设颗粒细胞作为巧合 探测器，并需要几乎同时激活至少两个 苔藓纤维输入，以释放动作电位。 他们将 还检查了颗粒细胞的内在放电，以及颗粒细胞的作用。 Golgi细胞抑制在调节通过这些细胞的传播中的作用 细胞在第二个目标中，我们假设平行纤维 侧手翻细胞和锥体细胞上的突触是突触的一个部位， 可塑性，我们将研究的具体要求， 钙升高，神经递质受体活化， 蛋白激酶C的激活可能是长期变化的基础， 突触功能在第三个目标中，我们将研究如何进入 突触后电位整合在树突树中， 锥体细胞和侧手翻细胞。研究人员假设， 这些细胞中树突状分支的不同模式， 在树突中存在活性的依赖性通道， 与突触整合的不同特征相关， 来自它们共同的来源，平行纤维。 他们将 确定树突状中存在的电导的位置和类型 树木使用光学成像技术，并将比较的特点， 在两种细胞类型中使用一种细胞的局灶性激活的突触整合 两个离散的平行纤维簇输入到树突状细胞 树在不同的条件下 所有这些实验都利用了 大脑中可视化和识别的神经元的密封记录 切片，一些实验也利用时域 对装载有荧光离子敏感染料的单细胞进行成像。的 这些实验的结果将帮助我们了解关键的细胞 神经整合输入信息的机制 通过颗粒细胞传递到耳蜗核 系统这些研究的结果将对 我们对耳蜗背侧信息处理的理解 核及其动力学特征，并可能提示新的功能 这个主要的听觉中心。这些研究也可能导致新的 了解信息处理的一般规则， 遍布大脑的神经元树突