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。功能性神经影像学是应对这一挑战的重要技术。在大鼠和小鼠中建立的大量人类大脑疾病动物模型使这些物种成为脑映射的理想候选者。然而，在传统的神经成像技术中，一个中心的困境是，为了避免运动伪影，必须使受试者固定，这会使最简单的行为消失。其结果是，对诸如攻击、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，完全植入式输液泵，在自由移动的动物，允许静脉推注管理成像放射性示踪剂通过远程激活。现在，随着原理的证明和泵的工作模型的使用，在科学界广泛应用和使用这项技术仍然需要一些关键的里程碑。我们现在提出了一种新的微团注输注泵（MIP），这将允许更大的灵活性，在广泛的实验环境中的工具。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向MIP供电，该功率链路由新型E类发射器驱动到外部谐振感应线圈。这将允许MIP被远程供电和触发，并且将使设备独立于有限的电池功率。对于在开放笼范例中使用MIP，我们建议使用电池，可在动物的家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。在这种设计中，频率选通的光学控制器将允许从几米的距离经皮触发MIP，对环境光不敏感。为了使MIP在小鼠中使用，我们建议设计一个微型的，加压的液体储存器和药物喷射室，并开发和验证一个微型减压阀。MIP在自由活动的大鼠以及小鼠中脑映射的应用将在小桌面实验范例（条件性恐惧反应）以及开放笼研究（Morris水迷宫）中进行测试。将使用[14 C]-碘安替比林注射，然后进行放射自显影，评估脑血流相关示踪剂分布。该研究由一个跨学科团队进行，旨在开发一种工具，该工具不仅可以应用于正常和异常行为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.