Source of ROS in Hippocampal Plasticity and Memory

描述（由申请人提供）：我们的实验室有兴趣了解突触可塑性和记忆形成的分子机制。我特别感兴趣的是活性氧（ROS）在这些过程中发挥的作用。ROS的实例是超氧化物、过氧化氢和一氧化氮（也称为活性氮物质）。已知ROS参与由氧化应激引起的神经变性;然而，也有相当多的证据表明ROS在信号转导中的作用。我们已经表明，活性氧是必要的突触可塑性和记忆的形成，但它不是很好地理解所需的活性氧是如何产生的。我感兴趣的是确定ROS是如何以受控的方式产生的，这样它们就可以在突触可塑性和记忆形成过程中用作信号分子，同时避免产生神经退行性疾病。在我的研究中，我将集中精力确定NADPH氧化酶是否是突触可塑性和记忆形成过程中ROS产生的主要来源。因此，我推测NADPH氧化酶产生的活性氧是突触可塑性和记忆形成所必需的。我建议使用野生型和基因敲除小鼠的神经药理学、电生理学和行为学分析来检验这些假设。

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.