PHYSIOLOGY OF DORSAL COCHLEAR NUCLEUS MOLECULAR LAYER

我们的长期目标是理解 中枢神经细胞的信息处理能力 系统。这项提案的目标是研究 听觉脑干某一区域的信息处理 耳蜗背核(DCN)。在这个最肤浅的层面 核，一个由细小的、无髓鞘的平行纤维组成的系统( 颗粒细胞)在主投射上形成大量突触 核内神经元(锥体细胞)和小中间神经元 (侧翻和星状细胞)。平行的光纤提供了 用于与发生在垂直于 DCN的音调轴。 关于信息加工机制的四个具体假说 将对哺乳动物DCN中的神经元进行研究。首先，我们将 研究一种假设，即特定子集的激活 兴奋性氨基酸受体，N-甲基-D-天冬氨酸(NMDA) 受体，可促进平行纤维的非线性易化 和听神经传入锥体细胞。第二，我们将 研究突触后钙离子内流与 具有平行的纤维突触活性，通过NMDA受体或 电压敏感型钙通道，可导致长期 突触或电压依赖性电导的修饰 突触后细胞。第三，我们将检验假设，电压- 耳蜗背核锥体细胞的依赖性放电模式 部分是由瞬间的钾电导产生的。第四，我们 将检验这样的假设，即车轮细胞抑制 锥体细胞。检验这些假说的实验使用 细胞内、全细胞紧密密封、场电位记录，以及 离体脑切片钙活性的光学记录 的制备和全单元密封式电压钳记录 非常孤立的神经元。 这些研究的结果将提供关于 平行纤维系统在耳蜗核的功能，以及 将有助于产生关于这个系统所扮演的角色的新理论 在处理传入的声学信息时。这些实验还将 为随后调查中环的变化奠定基础 可能作为周围声创伤的函数而发生的生理学 和衰老。

Our long term goals are to understand the principles which underlie the information processing capabilities of neurons in the central nervous system. The goal of this proposal is to examine mechanisms of information processing in one region of the auditory brainstem, the dorsal cochlear nucleus (DCN). In the most superficial layer of this nucleus, a system of fine, unmyelinated parallel fibers (axons of granule cells) make numerous synapses on the principal projection neurons of the nucleus (pyramidal cells) and on small interneurons (cartwheel and stellate cells). The parallel fibers provide the substrate for unique and extensive interactions occurring orthogonal to the tonotopic axis of the DCN. Four specific hypotheses about the mechanisms of information processing by neurons in the mammalian DCN will be investigated. First, we will investigate the hypothesis that the activation of a specific subset of excitatory amino acid receptors, the N-methyl-D-aspartate (NMDA) receptors, can contribute to nonlinear facilitation of parallel fiber and auditory nerve inputs to pyramidal cells. Second, we will investigate the hypotheses that postsynaptic calcium entry associated with parallel fiber synaptic activity, either through NMDA receptors or voltage-sensitive calcium channels, can result in the long-term modification of synaptic or voltage-dependent conductances in postsynaptic cells. Third, we will test the hypothesis that the voltage- dependent discharge patterns of dorsal cochlear nucleus pyramidal cells are in part produced by a transient potassium conductance. Fourth, we will test the hypothesis that cartwheel cells are inhibitory to pyramidal cells. The experiments to test these hypotheses use intracellular, whole-cell tight-seal, field potential recordings, and optical recordings of calcium activity from an in vitro brain slice preparation, and whole-cell tight-seal voltage-clamp recordings from acutely isolated neurons. The results of these studies will provide important information about the function of the parallel fiber system in the cochlear nucleus, and will help to generate new theories about the role that this system plays in processing incoming acoustic information. These experiments will also set the stage for subsequent investigations of changes in central physiology that may occur as a function of peripheral acoustic trauma and aging.