Imaging Unconditioned Fear

描述(申请人提供)：应用功能磁共振成像(FMRI)可视化涉及情绪的大脑区域，极大地提高了我们对人类神经生物学的理解。在将这种方法应用于有意识的动物方面，进展要慢得多，因为磁铁中的静止不动，以及在黑暗、狭窄、水平的空间内执行任务的能力等障碍。最近发明了一种小型动物抱持装置，用于对体重在300-500克之间的完全清醒的啮齿动物进行功能磁共振成像，从而克服了这些障碍。由于fMRI研究范式现在可以在动物身上进行，而不会造成伤害或牺牲，它们为在脑功能的多个时间点可以非侵入性地进行评估的领域的研究提供了新的研究机会，从而允许进行空间和时间映射。这项建议描述了一种新的方法，用fMRI来定位麻醉大鼠的恐惧反应。这些研究将使用功能磁共振成像来识别和监测与恐惧相关的神经元激活。对于大多数动物来说，引发恐惧的主要事件是被捕食者攻击的可能性。因此，目前正在实验室条件下模拟捕食者应激，以触发动物的无条件(天生)恐惧反应。最近的报告表明，动物神经内分泌状态的变化可能是恐惧反应的核心。此外，药物干预策略指出了这种情绪背后的神经系统的内在可塑性。为了测试这样一个假设，即由捕食者的气味引发的无条件恐惧将导致神经元激活的变化，以反映动物的神经内分泌状态和药物反应，我们将利用技术进步在清醒的动物身上进行非侵入性的功能磁共振成像。这项研究的长期目标是了解调节恐惧的中枢机制的独特特征，以及神经内分泌和神经药物状态对这种情绪处理的影响。由于所有动物都会经历恐惧，这些研究可能会扩大我们对焦虑和恐惧症的总体理解。

DESCRIPTION (provided by applicant): The application of functional magnetic resonance imaging (fMRI) to visualize brain regions involved in emotion has considerably improved our understanding of human neurobiology. Progress has been much slower in applying this approach to conscious animals, due to obstacles such as immobility in the magnet and ability to perform tasks within a dark, narrow, horizontal space. These obstacles have been overcome with the recent invention of a small animal holding device for performing fMRI on fully awake rodents ranging in weight from 300 - 500g. Since fMRI research paradigms can now be performed in animals without injury or sacrifice, they provide new research opportunities for studies in areas where multiple time points in brain functioning can be assessed non-invasively, thereby allowing spatial as well as temporal mapping. This proposal describes a novel approach for mapping the fear response in the anaesthetized rat with fMRI. These studies will use fMRI to identify and monitor neuronal activation associated with fearfulness. For most animals, a primary fear-eliciting event is the possibility of being attacked by a predator. Consequently, predator stress is currently being simulated under laboratory conditions to trigger unconditioned (innate) fear responses in animals. Recent reports suggest that changes in neuroendocrine status of an animal may be central to fear response. In addition, drug intervention strategies have pointed to the inherent plasticity of the neural systems underlying this emotion. To test the hypothesis that unconditioned fear triggered by the scent of a predator will result in alterations in neuronal activation in a manner that reflect the neuroendocrine status and pharmacological response of an animal, we will utilize the technological advances for performing fMRI non-invasively in a conscious animal. The long-term goal of this research is to provide an understanding of the unique features of central mechanisms that regulate fearfulness and the impact of the neuroendocrine and neuropharmacological status on the processing of this emotion. Since fear experience by all animals, these studies may expand our understanding of anxiety and phobias in general.