Homeostatic regulation of ion currents and neuronal net

描述(由申请人提供)：本项目旨在阐明 允许神经网络产生稳定输出的细胞机制，同时 保持应对扰动的灵活性，例如发生的扰动 在成长、学习、感官输入和损伤期间。离子流产生了 表征神经元活动的电学变化，以及单个神经元 而神经网络负责行为的产生。在苏中 在这种情况下，神经系统及其部分通常能够保持内稳态 在受到干扰或损坏后恢复它们的性能。几种机制 允许表达这种稳定或恢复活动的过程， 其中研究最多的可能是突触的可塑性。然而，一个不同的 机制正在成为表达的有力候选者 这两个看似自相矛盾的方面是神经元活动的灵活性和 稳定性。这种机制是对电压敏感的活性依赖的调节。 离子流。 在这个方案中，描述了一系列实验来研究其性质 这一鲜为人知的神经元活动调节机制。这 机制可能非常重要，因为它可能是一种新形式的 学习和记忆通过其对神经网络活动的稳定作用。这个 对小的和特征良好的神经网络的活动的调节，如 以及长期依赖于活性的离子电流调节的作用 在这一过程中将被调查。以前的工作已经显示出一些证据表明 不同离子流之间的长期相互作用和相互调节。 我将深入调查这些相互监管的相互作用及其 在稳定神经元活动的过程中可能起到作用。这个 实验方法将包括几种电生理模式 在体外记录完整网络中的神经元 生活在自由活动的动物中，在培养中的分离细胞中，在 长期的全网文化。药理操作也是如此 作为最近克隆的离子通道的RNA注射，将被用于修饰 内源性离子电流的表达。

DESCRIPTION (provided by applicant): This project aims to elucidate the cellular mechanisms that allow a neural network to produce stable output while retaining the flexibility to respond to perturbations, such as those that occur during growth, learning, sensory input and injury. Ionic currents produce the electrical changes that characterize neuronal activity, and individual neurons and neural networks are responsible for the generation of behavior. In so doing, the nervous system and its parts are often capable of homeostatically restoring their properties after a perturbation or damage. Several mechanisms allow this process of stabilization or restoration of activity to be expressed, the best studied of which is perhaps synaptic plasticity. However, a different mechanism is emerging as a powerful candidate to underlie the expression of these two seemingly paradoxical aspects of neuronal activity of flexibility and stability. This mechanism is activity-dependent regulation of voltage-sensitive ionic currents. In this proposal a series of experiments is described to study the properties of this poorly understood mechanism of neuronal activity regulation. This mechanism is potentially of great importance as it may underlie a new form of learning and memory via its stabilizing effect on neural network activity. The regulation of activity in a small and well-characterized neural network, as well as the role of long-term activity-dependent regulation of ionic currents in this process will be investigated. Previous work has shown some evidence of long-term interactions and mutual regulation between different ionic currents. I will investigate in depth these mutual regulatory interactions and their possible role in the process of stabilization of neuronal activity. The experimental methodology will include several modes of electrophysiological recording of neurons in the intact network in vitro, in the intact network in the living a freely moving animal, in dissociated cells in culture, and in long-term culture of the whole network. Pharmacological manipulations, as well as RNA injections of recently cloned ionic channels, will be used to modify the expression of endogenous ionic currents.