RUI: Mechanisms of Synchronized Oscillatory Activity in the Nervous System

节律性运动行为的基本模式是由称为神经振荡器的中枢神经系统回路产生的。在这项研究中，由钙电流抑制引起的振荡活动是不寻常的，因为它依赖于钠电流（而不是在其他动物中观察到的钙电流），并且因为振荡在同一无脊椎神经系统的所有神经元中同步发生。这些新颖的特征将使几个具有广泛意义的问题得以解决。首先，是什么细胞机制产生了这些钠依赖性振荡，为什么钠依赖性振荡与钙依赖性振荡相比如此罕见？第二，什么细胞机制被用来同步神经网络中的振荡活动？为了回答这些问题，Angstadt博士将1)开发一种独立的神经元制备，表达类似于在完整神经节中观察到的振荡活动，2)识别和表征持续离子电流在产生振荡中的作用，3)确定负责同步不同神经元中振荡的细胞机制。他的方法是从无脊椎动物神经节中移除已识别的神经元，在细胞培养中分离这些神经元，并使用电压钳技术研究它们的离子电流。在其他实验中，振荡同步的机制将在完整的神经节实验中进行研究。这些研究很重要，因为它们将进一步了解神经细胞中的持续钠传导，包括它们在振荡活动产生中的功能作用，并可能为研究与癫痫和其他更复杂的神经系统中癫痫发作相关的同步神经元活动的细胞机制提供模型系统。

The basic patterns of rhythmic motor behavior are generated by central nervous system circuits called neural oscillators. The oscillatory activity under investigation in this study, induced by suppression of calcium currents, is unusual in that it depends on sodium currents (rather than calcium currents as observed in other animals) and because the oscillations occur synchronously in all neurons of the same invertebrate nervous systems. These novel features will allow several questions of broad significance to be addressed. First, what cellular mechanisms generate these sodium-dependent oscillations and why are sodium-dependent oscillators so rare compared to calcium-dependent oscillators? Second, what cellular mechanisms are used to synchronize oscillatory activity within neural networks? To answer these questions, Dr. Angstadt will 1) develop an isolated neuron preparation that expresses oscillatory activity similar to that observed in intact ganglia, 2) identify and characterize the role of persistent ionic currents in generating the oscillations, and 3) determine the cellular mechanisms responsible for synchronizing the oscillations in different neurons. His approach will be to remove identified neurons from invertebrate ganglia, isolate these neurons in cell culture, and study their ionic currents using voltage clamp techniques. In other experiments, mechanisms underlying synchronization of oscillations will be investigated in experiments on intact ganglia. These studies are important because they will further understanding of persistent sodium conductances in nerve cells, including their functional role in the generation of oscillatory activity, and may provide a model system for studies of cellular mechanisms underlying the synchronized neuronal activity associated with epileptic and other seizures in more complex nervous systems.