Microinfusion Pump For Animal Functional Brain Mapping

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。功能神经成像是迎接这一挑战的一项关键技术。已经在大鼠和小鼠身上建立的大量人类大脑疾病的动物模型使这些物种成为脑部测绘的理想对象。然而，在传统的神经成像技术中，一个核心的两难境地是，为了避免运动伪影，对受试者的固定是必要的，除了最简单的行为外，所有其他行为都会消失。其结果是，攻击性、交配、进食和恐惧等核心动物行为的大脑功能仍然知之甚少。为了解决固定的问题，我们最近开发了一种微型、自给式、完全可植入的输液泵，在自由活动的动物中，它可以通过远程激活静脉推注成像放射性示踪剂。现在，随着原理的证明和泵的工作模式的使用，一些关键的里程碑仍然是在科学界广泛应用和使用这项技术所必需的。我们现在提出一种新型微丸输液泵(MIP)，它将使该工具在广泛的实验环境中具有更大的灵活性。对于小型桌面实验范例中的应用，我们建议通过经皮射频功率链路连接到由新型E类发射机驱动的外部谐振感应线圈来为MIP供电。这将允许MIP被远程供电和触发，并将使该设备独立于有限的电池功率。为了在开笼范例中使用MIP，我们建议使用电池，在动物的家中使用射频电源连接进行充电，使MIP在动物自由漫游时也能独立运行。这种设计中的频率选通光学控制器将允许在几米远的距离内经皮触发MIP，对环境光不敏感。为了将MIP小型化以供小鼠使用，我们建议设计一种微型加压液体储液器和药物喷射室，并开发和验证一种微型电热阀。将MIP应用于自由活动大鼠和小鼠的脑成像将在小型桌面实验范式(条件性恐惧反应)以及开放笼子研究(Morris水迷宫)中进行测试。脑血流相关示踪剂的分布将使用[14C]-安替比林注射和放射自显影进行评估。研究是由一个跨学科团队进行的，目的是开发一种工具，该工具不仅可以应用于正常和异常行为背后的基本神经元回路的大脑映射，还可以应用于小动物模型的行为药理学和体内生理学研究。

DESCRIPTION (provided by applicant): Understanding the relationship between behavior and underlying brain function constitutes one of the most complex intellectual challenges today. Functional neuroimaging represents an essential technology toward meeting this challenge. The large number of animal models of human brain disorders that have been established in rats and mice makes these species ideal candidates for brain mapping. A central dilemma, however, in conventional neuroimaging techniques is that immobilization of the subject, necessary to avoid movement artifact, extinguishes all but the simplest behaviors. The result is that brain function of such core animal behaviors as aggression, mating, feeding, and fear, remains poorly understood. To address the problem of immobilization, we have recently developed a miniature, self-contained, fully implantable infusion pump that in freely-moving animals allows intravenous bolus administration of imaging radiotracers by remote activation. Now with proof of principle demonstrated and a working model of the pump in use, a number of critical milestones remain necessary for widespread application and use of this technology in the scientific community. We now propose a novel microbolus infusion pump (MIP) that will allow greater flexibility of this tool in a broad range of experimental environments. For applications in small table-top experimental paradigms, we propose to power the MIP by a transcutaneous radiofrequency power link to an external resonating inductive coil driven by a novel Class E transmitter. This will allow the MIP to be powered and triggered remotely, and will make the device independent of finite battery power. For use of the MIP in open cage paradigms, we propose the use of a battery, rechargeable in the animal's homecage using the radiofrequency power link that enables the MIP to also operate independently when the animal is roaming free. A frequency-gated, optical controller in this design will allow transcutaneous triggering of the MIP from several meters distance, insensitive to ambient light. To miniaturize the MIP for use in mice, we propose to design a miniature, pressurized liquid reservoir and drug ejection chamber, and to develop and validate a miniature electrothermal valve. Application of the MIP to brain mapping in freely moving rats, as well as mice will be tested in a small table-top experimental paradigm (Conditioned Fear Response), as well as in an open cage study (Morris Water Maze). Cerebral blood flow related tracer distribution will be assessed using [14C]-iodoantipyrine injections followed by autoradiography. Research is conducted by an interdisciplinary team to develop a tool that can be applied not only to the brain mapping of basic neuronal circuits underlying normal and abnormal behavior, but also to behavioral pharmacology and in-vivo physiologic studies in small animal models.