Source of ROS in Hippocampal Plasticity and Memory

描述(申请人提供)：我们的实验室对了解突触可塑性和记忆形成的分子机制感兴趣。我特别感兴趣的是活性氧(ROS)在这些过程中所起的作用。ROS的例子是超氧化物、过氧化氢和一氧化氮(也称为活性氮物种)。众所周知，ROS参与了氧化应激引起的神经退行性变；然而，也有相当多的证据表明ROS在信号转导中发挥作用。我们已经证明ROS是突触可塑性和记忆形成所必需的，但是我们还不能很好地理解所需的ROS是如何产生的。我感兴趣的是确定ROS是如何以受控的方式产生的，以便它们可以在突触可塑性和记忆形成过程中用作信号分子，同时避免神经退行性疾病的产生。在我的研究中，我将专注于确定NADPH氧化酶是否是突触可塑性和记忆形成过程中产生ROS的主要来源。因此，我推测NADPH氧化酶产生的ROS在突触可塑性和记忆形成过程中是必需的。我建议通过对野生型和基因敲除小鼠的神经药理学、电生理学和行为分析来验证这些假说。

DESCRIPTION (provided by applicant): Our lab is interested in understanding the molecular mechanisms underlying synaptic plasticity and memory formation. I am specifically interested in the role that reactive oxygen species (ROS) play in these processes. Examples of ROS are superoxide, hydrogen peroxide, and nitric oxide (also known as a reactive nitrogen species). ROS are known to be involved in neurodegeneration caused by oxidative stress; however there is also considerable evidence for a role of ROS in signal transduction. We have shown that ROS are necessary for synaptic plasticity and memory formation, yet it is not well understood how the required ROS are generated. I am interested in determining how ROS are generated in a controlled manner such that they can be utilized as signaling molecules during synaptic plasticity and memory formation while avoiding the generation of neurodegenerative conditions. In my studies, I will concentrate on determining whether NADPH oxidase is the principle source for ROS production during synaptic plasticity and memory formation. Thus, I hypothesize that that ROS generated by NADPH oxidase is required during synaptic plasticity and memory formation. I propose to test these hypotheses using neuropharmacological, electrophysiological, and behavioral analysis of wild-type, and knockout mice.