Microinfusion Pump For Animal Functional Brain Mapping

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。功能性神经成像是应对这一挑战的一项重要技术。在大鼠和小鼠身上建立的大量人类大脑疾病动物模型使这些物种成为大脑测绘的理想候选者。然而，在传统的神经成像技术中，一个主要的难题是，为了避免运动伪影，必须固定受试者，但除了最简单的行为外，它会消除所有行为。结果是，诸如攻击、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的、独立的、完全植入式的输液泵，它可以在自由运动的动物中通过远程激活来静脉注射成像放射性示踪剂。现在，随着原理的证明和泵的工作模型的使用，该技术在科学界的广泛应用和使用仍然需要一些关键的里程碑。我们现在提出了一种新的微丸输液泵（MIP），它将允许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的应用，我们建议通过经皮射频电源连接到由新型E类发射器驱动的外部谐振电感线圈，为MIP供电。这将允许MIP远程供电和触发，并将使设备独立于有限的电池电量。对于在开放式笼子范例中使用MIP，我们建议使用电池，在动物的笼子中使用射频电源链路充电，使MIP在动物自由漫游时也能独立运行。该设计中的频率门控光学控制器将允许从几米远的地方经皮触发MIP，对环境光不敏感。为了使MIP小型化，我们建议设计一个微型加压储液器和药物弹射室，并开发和验证一个微型电热阀。将MIP应用于自由活动的大鼠和小鼠的脑图绘制，将在小型桌面实验范式（条件恐惧反应）和开放式笼子研究（莫里斯水迷宫）中进行测试。脑血流相关的示踪剂分布将通过[14C]-碘安替比林注射和放射自显影来评估。该研究由一个跨学科团队进行，旨在开发一种工具，不仅可以应用于正常和异常行为背后的基本神经回路的大脑图谱，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.