PET Behavioral Brain Mapping In Freely Moving Animals

描述(由申请人提供)：理解行为和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。动物行为的功能神经成像的一个中心难题是，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，这使得除了最简单的活动之外，所有的活动都消失了，并引入了束缚应激的额外变量。结果是，哺乳动物的核心行为，如攻击性、交配、觅食和社会互动--都需要运动--的大脑功能仍然知之甚少。如果以非搅动的方式给药一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大脑区域激活进行成像，则行为约束问题可以得到解决。我们之前已经设计了一种植入式微型输液泵(MIP)，用于给药放射性示踪剂。我们现在建议将这项技术应用于[64Cu]-PTSM的管理，这是一种用于PET应用的新型单程提取脑血流(CBF)示踪剂。具体目的是：1)在动物模型中，用双标记放射自显影技术比较[~(64)Cu]-PTSM和经典的[~(14)C]-安替比林脑血流示踪剂的相对局部分布。2)应用正电子发射计算机断层扫描(PET)技术验证[64Cu]-PTSM在MIP给药时可用于评估标准运动挑战期间自由活动动物的脑功能激活情况。在这里，无论是在跑步机上行走还是在静止的控制条件下，都可以通过MIP泵给药。在完成行为任务和捕获示踪剂后，使用PET对大脑的区域激活进行成像。将便携式输液泵应用于[64Cu]-PTSM的给药有望使PET用于自由活动受试者的功能性神经成像范例-这在以前使用传统的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。这样的知识可以为在精神障碍的背景下改进功能大脑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.