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）：理解行为与潜在大脑功能之间的关系是当今最复杂的智力挑战之一。动物行为功能性神经成像的一个核心困境是，使用正电子发射断层扫描 (PET)、单光子发射计算机断层扫描 (SPECT) 和功能性磁共振成像 (fMRI) 的传统神经成像方案通常依赖于受试者的固定，这消除除了最简单的活动之外的所有活动，并引入约束压力的附加变量。结果是，人们对攻击、交配、觅食和社交互动等哺乳动物核心行为（所有这些都需要运动）的大脑功能仍然知之甚少。如果通过非搅动方式施用单次提取放射性示踪剂，并且在完成行为任务和捕获示踪剂后对区域大脑激活进行成像，则可以解决行为限制的问题。我们之前设计了一种用于放射性示踪剂管理的植入式微型输液泵（MIP）。我们现在建议将此技术应用于 [64Cu]-PTSM 的管理，这是一种用于 PET 应用的新型单通道提取脑血流 (CBF) 示踪剂。具体目标是： 1) 在动物模型中，通过双标记放射自显影比较 [64Cu]-PTSM 与经典灌注示踪剂 [14C]-碘安替比林的相对区域 CBF 示踪剂分布。 2) 使用 PET 验证 [64Cu]-PTSM 当由 MIP 管理时可用于评估自由活动动物在执行标准化运动挑战期间的功能性大脑激活。这里，[64Cu]-PTSM 在跑步机行走期间或静态控制条件期间由 MIP 泵管理。完成行为任务并捕获示踪剂后，使用 PET 对区域大脑激活进行成像。将便携式输液泵应用于 [64Cu]-PTSM 的管理有望允许使用 PET 在自由活动的受试者中进行功能性神经成像范例 - 这在以前使用传统神经成像方案是不可行的。这些方法的未来应用有望增加我们对正常行为的基本组成部分的理解。这些知识可以为精神障碍背景下功能性大脑解剖结构的改进整合提供基础。