Optical Tomography of Multiple Parallel Memory Systems in Freely Moving Rats

描述(申请人提供)：50多年来，人们已经知道，基于经验的行为变化(即学习)和存储此类变化的机制至少有两种形式，一种基于海马体(阿尔茨海默氏症中受损的结构)，另一种位于海马体之外。最近，有一点变得很清楚，即有多个记忆区域，包括海马体、杏仁核和纹状体，它们并行地、有时合作地、有时竞争地控制行为。包括fMRI和PET扫描在内的现代成像方法已经表明，这种多重记忆系统的概念不仅适用于人类，也适用于其他哺乳动物物种，并随着学习的进行揭示了记忆组织的重要方面。不幸的是，功能磁共振成像和正电子发射计算机断层扫描方法极其昂贵，而且只能用于固定或麻醉的受试者。因此，我们的研究计划是使用一种新的光学断层扫描模型来检测自由移动的大鼠学习过程中记忆结构的变化。这种“漫反射光学断层扫描”(DOT)方法使我们能够观察到由fMRI测量的相同的血流动力学变量。因为我们可以通过使用两个波长来检测氧合和脱氧-血红蛋白，所以我们可以看到血液动力学大脑状态的一些方面，这是目前的fMRI方法不可能的。我们打算将这些功能与EEC记录并行使用，以寻找在老鼠学习三种不同任务时，三个不同记忆区域预计会发生的变化。先前的损伤研究使我们预计，海马体将在一个任务中优先激活，杏仁核在第二个任务中被激活，背侧纹状体在第三个任务中被激活。这项有希望的工作的成功结果将构成一个新研究领域的开始，该领域将清醒、自由活动的动物的断层成像与人类无法实现的实验方法相结合。我们预计，拟议的工作将直接用于病理大脑状态的分析，并将在短期内应用于癫痫、阿尔茨海默病和其他神经系统损伤的动物模型。

DESCRIPTION (provided by applicant): It has been known for more than 50 years that experience-based changes in behavior (i.e., learning) and the mechanisms that store such changes come in at least two forms, one based in the hippocampus (a structure damaged in Alzheimer's Disease) and one outside the hippocampus. More recently, it has become clear that there are multiple memory areas, including the hippocampus, amygdala and striatum, which act in parallel, sometimes in cooperation, sometimes in competition, to control behavior. Modern imaging methods, including fMRI and PET scanning, have shown that this multiple memory system concept applies to humans as well as to other mammalian species, and have revealed important aspects of memory organization as learning proceeds. Unfortunately, the fMRI and PET methods are extremely expensive and, moreover, can be used only in immobilized or anesthetized subjects. Accordingly, our research plan is to use a novel, optical tomographic model to detect changes in memory structures in the course of learning by freely moving rats. This "diffuse optical tomography" (DOT) method permits us to look at the same hemodynamic variables measured by fMRI. Because we can detect oxy- and well as deoxy-hemoglobin by using 2 wavelengths, we can see aspects of the hemodynamic brain state not possible with current fMRI methods. We intend to use these capabilities in parallel with EEC recordings to look for changes that are expected to occur in three different memory areas while rats learn three different tasks. Prior lesion studies lead us to expect that the hippocampus will be preferentially activated in one task, the amygdala in a second, and the dorsal striatum in the third. A successful outcome to this promising work will constitute the beginning of a new study area that combines tomographic imaging in awake, freely moving animals with experimental methods impossible with humans. We anticipate that the proposed work will be of direct use in the analysis of pathological brain states and will in short order be applied to animal models of epilepsy, Alzheimer's Disease and other impairments of the nervous system.