Homeostatic regulation of ion currents and neuronal net

描述（由申请人提供）：本项目旨在阐明 细胞机制允许神经网络产生稳定的输出， 保持灵活性，以应对扰动，如发生 在生长、学习、感觉输入和损伤过程中。离子电流产生 表征神经元活动的电变化， 而神经网络负责行为的产生。这样 做，神经系统及其部分往往能够自我平衡 在扰动或损坏后恢复其特性。几种机制 允许表达这种稳定或恢复活动的过程， 其中研究得最多的可能是突触可塑性。然而，一个不同的 机制正在成为一个强有力的候选人，以支持表达， 神经元活动的这两个看似矛盾的方面， 稳定这种机制是活性依赖性调节电压敏感的 离子流 在这一建议中，一系列的实验描述了研究性质 神经元活动调节机制知之甚少。这 机制可能非常重要，因为它可能是一种新形式的 通过其对神经网络活动的稳定作用来学习和记忆。的 在一个小的和特征良好的神经网络中调节活动，如 以及离子电流的长期活性依赖性调节的作用 在这个过程中，将进行调查。以前的研究已经显示了一些证据， 不同离子电流之间的长期相互作用和相互调节。 我将深入研究这些相互调节的相互作用及其 在稳定神经元活动的过程中可能发挥作用。的 实验方法将包括几种电生理模式 记录体外完整网络中的神经元， 活的自由移动的动物，在培养的解离细胞中， 全网长期文化。药物操作，以及 作为最近克隆的离子通道的RNA注射，将用于修饰 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.