Source of ROS in Hippocampal Plasticity and Memory

描述（申请者提供）：本实验室主要研究突触可塑性和记忆形成的分子机制。我对活性氧（ROS）在这些过程中的作用特别感兴趣。ROS的例子有超氧化物、过氧化氢和一氧化氮（也称为活性氮）。已知ROS参与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活性氧在信号转导中的作用。我们已经证明，活性氧是突触可塑性和记忆形成所必需的，但目前还不清楚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被用作信号分子，同时避免神经退行性疾病的产生。在我的研究中，我将集中研究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，我假设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。我建议用神经药理学、电生理学和野生型和基因敲除小鼠的行为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.