PET Behavioral Brain Mapping In Freely Moving Animals

描述（由申请人提供）：理解行为和潜在大脑功能之间的关系是当今最复杂的智力挑战之一。动物行为的功能性神经成像的一个核心难题是，传统的神经成像方案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）和功能磁共振成像（fMRI），通常依赖于固定受试者，这消除了除最简单的活动外的所有活动，并引入了约束应力的额外变量。结果是，对核心哺乳动物行为的大脑功能，如侵略、交配、觅食和社会互动——所有这些都需要运动——仍然知之甚少。如果以非鼓动的方式进行单次提取放射性示踪剂，并在完成行为任务和捕获示踪剂后对脑区域激活进行成像，则可以解决行为约束问题。我们之前设计了一种可植入的微型输液泵（MIP），用于放射性示踪剂的管理。我们现在建议将该技术应用于[64Cu]-PTSM的管理，这是一种用于PET应用的新型单道提取脑血流（CBF）示踪剂。具体目的是：1)通过双标记放射自显影比较[64Cu]-PTSM与经典灌注示踪剂[14C]-碘安替比林在动物模型中的相对区域分布。2)通过PET验证[64Cu]-PTSM在MIP管理下可用于评估自由运动动物在标准化运动挑战期间的功能性脑激活。在这里，[64Cu]-PTSM由MIP泵在跑步机行走或静止控制条件下进行管理。在完成行为任务和捕获示踪剂后，使用PET成像脑区域激活。便携式输注泵在[64Cu]- ptsm管理中的应用，有望使PET在自由运动受试者的功能神经成像范式中得到应用，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构建块的理解。这些知识可能为在精神障碍的背景下改进脑功能解剖学的整合提供基础。

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.