PET Behavioral Brain Mapping In Freely Moving Animals

自由活动动物的 PET 行为大脑图谱

• 批准号: 6992702
• 负责人: DANIEL PHILIPP HOLSCHNEIDER
• 金额: $ 21.46万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6992702
• 关键词: behavioral /social science research tag; bioimaging /biomedical imaging; biological models; body movement; brain circulation; brain imaging /visualization /scanning; brain mapping; cats; computed axial tomography; copper; gait; implant; miniature biomedical equipment; neuromuscular function; neuropsychological tests; neuropsychology; perfusion; positron emission tomography; radiotracer; technology /technique development

DESCRIPTION (provided by applicant): Understanding the relationship between behavior and underlying brain function constitutes one of the most complex intellectual challenges today. A central dilemma in functional neuroimaging of animal behaviors has been the fact that conventional neuroimaging protocols using positron emission tomography (PET), single photon emission computer tomography (SPECT) and functional magnetic resonance imaging (fMRI) generally rely on immobilization of the subject, which extinguishes all but the simplest activity and introduces the additional variables of restraint stress. The result is that brain function of core mammalian behaviors such as aggression, mating, foraging and social interaction - all requiring locomotion - remains poorly understood. The problem of behavioral restraint can be solved if a single-pass extraction radiotracer is administered by non-agitating means, and regional brain activation is imaged after completion of the behavioral task and capture of the tracer. We have previously designed an implantable, miniature, infusion pump (MIP) for the administration of radiotracers. We now propose to apply this technology to the administration of [64Cu]-PTSM, a novel single-pass extraction cerebral blood flow (CBF) tracer used for PET applications. Specific aims are: 1) To compare in an animal model, the relative regional CBF tracer distribution of [64Cu]-PTSM to that of the classical perfusion tracer [14C]-iodoantipyrine by dual label autoradiography. 2) To validate using PET that [64Cu]-PTSM when administered by the MIP can be used for the assessment of functional brain activation in freely moving animals during performance of a standardized locomotor challenge. Here [64Cu]-PTSM is administered by the MIP pump during either treadmill walking or during a quiescent control condition. Regional brain activation is imaged using PET after completion of the behavioral task and capture of the tracer. Application of a portable infusion pump to the administration of [64Cu]-PTSM promises to allow use of PET to functional neuroimaging paradigms in freely-moving subjects - something that has previously not been feasible using conventional neuroimaging protocols. Future applications of these methods promise to increase our understanding of the basic building blocks of normal behavior. Such knowledge may provide the basis of an improved integration of a functional brain anatomy in the context of mental disorders.

描述（由申请人提供）：了解行为与潜在的大脑功能之间的关系构成了当今最复杂的智力挑战之一。动物行为功能神经影像学的核心困境是，使用正电子发射断层摄影（PET），单光子发射计算机断层扫描（SPECT）和功能磁共振成像（FMRI）的常规神经成像协议（PET）通常依赖于对主体的固定压力，而这些压力通常会散发出其他限制。结果是核心哺乳动物行为的大脑功能，例如侵略，交配，觅食和社会互动（所有需要运动）仍然很熟悉。如果通过非调节均值给予单次提取放射性示踪剂，则可以解决行为约束的问题，并且在完成行为任务并捕获示踪剂后会成像区域大脑激活。我们以前已经设计了一种可植入的，微型的输注泵（MIP），用于放射性示例。现在，我们建议将该技术应用于[64CU] -PTSM的给药，这是一种新型的单通萃取大脑血流（CBF）示踪剂，用于宠物应用。具体目的是：1）在动物模型中进行比较，即[64CU] -PTSM的相对区域CBF示踪剂分布与经典灌注示踪剂[14C] -Iodootoantipyrine通过双标记自显影术。 2）要使用PET验证通过MIP给药时[64CU] -PTSM可以用于评估在标准化的运动挑战的性能期间自由移动动物的功能性脑激活。这里[64CU] -PTSM在跑步机行走或静止控制条件下由MIP泵管理。在完成行为任务并捕获示踪剂后，使用PET对区域大脑的激活进行成像。将便携式输液泵应用于[64CU] -PTSM的给药中，有望在自由移动的受试者中使用PET在功能性神经影像学范式中使用 - 使用常规神经影像方案以前不可行。这些方法的未来应用有望增加我们对正常行为基本构件的理解。这种知识可以为在精神障碍的背景下改善功能性大脑解剖结构的整合提供基础。