Optical Tomography of Multiple Parallel Memory Systems in Freely Moving Rats

自由移动大鼠多个并行记忆系统的光学断层扫描

• 批准号: 7184882
• 负责人: ROBERT L MULLER
• 金额: $ 23.28万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7184882
• 关键词: Alzheimer' s Disease; Amygdaloid structure; Animal Model; Animals; Area; Attention; Behavior; Behavior Control; Behavioral; Brain; Cell Nucleus; Cells; Characteristics; Cognitive; Complement; Consensus; Corpus striatum structure; Data; Dissociation; Dorsal; Epilepsy; Fimbria of hippocampus; Functional Imaging; Functional Magnetic Resonance Imaging; Goals; Head; Hemoglobin; Hippocampus (Brain); Human; Image; Impairment; Influentials; Lateral; Lead; Learning; Left; Lesion; Literature; Localized; Measurement; Measures; Memory; Methodology; Methods; Modeling; Motor; Motor Skills; Nervous system structure; Neurobiology; Optical Tomography; Optics; Outcome; Patients; Performance; Plant Roots; Positioning Attribute; Positron-Emission Tomography; Process; Psychological reinforcement; Published Comment; Rattus; Research; Running; Sensory; Signal Transduction; Structure; System; Techniques; Testing; Time; Training; Upper arm; Video Recording; Week; Work; awake; base; behavioral pharmacology; blood oxygen level dependent; caudate nucleus; concept; cost; day; design; diffuse optical tomography; distributed memory; experience; hemodynamics; heuristics; novel; relating to nervous system; research study; response; tool

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.

描述（由申请人提供）：50多年来，人们已经知道，基于经验的行为变化（即学习）和存储这些变化的机制至少有两种形式，一种基于海马体（阿尔茨海默病中受损的结构），另一种基于海马体之外。最近，人们已经清楚地认识到，有多个记忆区域，包括海马体、杏仁核和纹状体，它们有时在合作中，有时在竞争中并行地起作用，以控制行为。包括功能磁共振成像和PET扫描在内的现代成像方法表明，这种多重记忆系统概念适用于人类和其他哺乳动物物种，并揭示了学习过程中记忆组织的重要方面。不幸的是，功能磁共振成像和PET方法非常昂贵，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颖的光学层析模型来检测自由运动大鼠在学习过程中记忆结构的变化。这种“漫射光学断层扫描”（DOT）方法允许我们观察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血红蛋白和脱氧血红蛋白，我们可以看到当前功能磁共振成像方法无法看到的血流动力学脑状态的各个方面。我们打算将这些功能与脑电图记录同时使用，以寻找当大鼠学习三种不同任务时，三个不同记忆区域可能发生的变化。先前的病变研究使我们期望海马体在一个任务中优先被激活，杏仁核在第二个任务中优先被激活，背纹状体在第三个任务中优先被激活。这项有希望的工作的成功结果将构成一个新的研究领域的开始，该研究领域将在清醒、自由活动的动物身上进行层析成像，并采用不可能在人类身上进行的实验方法。我们预计这项工作将直接用于病理脑状态的分析，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。