PHYSIOLOGY OF DORSAL COCHLEAR NUCLEUS MOLECULAR LAYER

描述(改编自《调查者摘要》)：背部 耳蜗核是一个相对复杂的神经区域，其功能 可以提供对复杂声学的快速和早期处理 刺激，并形成听觉和非听觉之间的联系 事件。拟议中的实验研究了细胞机制 在这个分子层的电路中的信息处理 原子核。这个回路由一组强制性的中间神经元组成， 颗粒细胞接受来自不同苔藓纤维的输入 传入，进而形成兴奋的平行纤维，支配两个 主要靶点：一组抑制性神经元、侧翻细胞和 核内的主要投射神经元是锥体细胞。这个 本提案的目标是跟踪发生在3个关键点上的转型 此回路中的点：在苔藓纤维颗粒细胞突触，在 平行纤维和它们的突触后靶之间的突触，以及在 突触后的细胞树突与平行纤维相连。在 第一个目标，苔藓纤维颗粒细胞突触的突触整合 将会被检查。他们假设颗粒细胞的作用是一致的 探测器，并且需要几乎同时激活至少两个 苔藓纤维的输入是为了放电动作电位。他们会 还观察了颗粒细胞的内源性放电及其作用 高尔基体细胞在调节通过这些细胞的传递中的抑制 细胞。在第二个目标中，我们假设平行光纤 车轮细胞和锥体细胞上的突触是突触的一个位置 可塑性，我们将研究对 钙升高，神经递质受体激活，以及 蛋白激酶C的激活可能是血管紧张素转换酶长期变化的基础 突触功能。在第三个目标中，我们将调查进入 哪些突触后电位整合在脑干的树突中 锥体细胞和手轮细胞。调查人员推测， 这些细胞中树突状分支的不同模式，以及 在它们的树突中存在有源电压依赖通道，将是 与突触整合的不同特征相关 它们的活动来自它们的共同来源，平行纤维。他们会的 确定枝晶中存在的导电位置和类型 使用光学成像技术的树木，并将比较 局灶性激活一种细胞在两种细胞类型中的突触整合 以及输入到树枝状结构的两个离散的平行纤维簇 树在不同的条件下。所有这些实验都利用 大脑中可见和已识别神经元的密封性记录 幼年大鼠的切片，一些实验也利用了时间域 单细胞的荧光离子敏感染料成像。这个 这些实验的结果将有助于我们理解关键的细胞 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。这些研究得出的结果将对 我们对背侧耳蜗区信息处理的认识 原子核及其动力学特征，并可能提出新的功能 对于这个主要的听觉中枢。这些研究还可能导致新的 关于信息处理的一般规则的知识 遍布大脑的神经元树突。

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.