SENSORY PATHWAYS UNDERLYING NEUROPEPTIDE REGULATION OF FOOD INTAKE

一般摘要探测和应对捕食者等威胁对生存至关重要，但也会中断维持能量所需的摄食行为。人们对觅食和躲避捕食者之间的权衡取舍的大脑机制知之甚少。因此，这项工作将研究大脑威胁如何以及在哪里抑制青蛙的食物消耗，这些青蛙拥有高度发达和易于访问的控制进食的神经回路。具体地说，实验将确定当动物遇到捕食者时，大脑中产生的一种化学物质如何扰乱刺激进食的感觉线索的处理，从而在行为不适应时抑制行为。这些研究符合美国的国家利益，因为它们将通过促进神经系统如何整合信息和产生行为的知识，以及神经科学研究的基本目标，以及它们对与焦虑相关的饮食障碍产生意想不到的洞察的潜力，来帮助保持我们作为科学和技术领导者的角色。这项工作还将通过以下方式影响科学教育：培训来自代表性不足群体的学生，这些学生将通过德克萨斯理工大学现有的项目招募；创建新的神经生理学实验室练习，以补充通过NSF资助的项目已经开发的练习；以及为NSF的国家案例研究教学中心生成新的案例研究。在外展方面，该团队将在德克萨斯理工博物馆创建一个关于猎物的感官检测和恐惧生态的博物馆展览，并向当地小学提供与两栖动物生物学、行为和保护有关的用品和材料。技术摘要这项工作的目标是根据指导最佳觅食的生态和进化力量来了解神经内分泌对食物摄入量的调节。具体地说，这项工作将确定应激神经肽促肾上腺皮质激素释放因子(CRF)调节多感官猎物捕获的神经机制(S)。在爪蛙非洲爪蛙中，CRF通过视顶盖内的调制迅速抑制猎物捕获，视顶盖是这种脊椎动物和其他脊椎动物对猎物和捕食者线索进行多感觉处理的重要大脑区域。PI现在将确定顶盖CRF R1受体是否抑制多感官引导的猎物捕获。在第一个目标中，将使用药理学和成像方法来测试顶盖CRF R1受体是否干扰与猎物捕获相关的侧线和/或视觉线索的处理。在第二个目标中，将研究感觉传入和抑制性GABA中间神经元在介导CRF抑制多感觉引导的猎物捕获中的作用。总之，这些实验将确定一种重要的饱腹肽干扰食物获取所需的多感官途径的机制。这些发现将广泛影响我们对厌恶行为的神经元基础及其在脊椎动物中的调节的理解，并可能阐明恐惧处理路径被扰乱的疾病的进化起源。与这项提议相关的工作也将直接纳入本科生的课堂和实验室教育经验，并将指导当地社区展品的发展。

General AbstractDetecting and responding to threats such as predators is critical for survival, but also interrupts feeding behaviors required to maintain energy. The brain mechanisms underlying foraging and predator avoidance trade-offs are poorly understood. This work will therefore investigate how and where within the brain threat inhibits food consumption in frogs that have a highly-developed and easily accessible neural circuitry that controls feeding. Specifically, experiments will determine how a chemical produced in the brain when animals encounter a predator disrupts the processing of sensory cues that stimulate feeding and thereby inhibits the behavior when it is not adaptive. The studies fall within US national interests in that they will help maintain our role as a leader in science and technology by advancing knowledge of how nervous systems integrate information and generate behavior, fundamental goals of neuroscience research, as well as in their potential to produce unexpected insight into anxiety-related eating disorders. The work will also impact science education through the training of students from underrepresented groups who will be recruited through existing programs at Texas Tech University, the creation of new neurophysiology laboratory exercises to complement those already developed through NSF-funded programs, and the generation of new case studies for the NSF's National Center for Case Study Teaching in Science. For outreach, the team will create a museum exhibit on sensory detection of prey and the ecology of fear at the Texas Tech Museum and provide supplies and materials related to amphibian biology, behavior and conservation to local elementary schools. Technical AbstractThe goal of this work is to understand neuroendocrine modulation of food intake in light of the ecological and evolutionary forces that guide optimal foraging. Specifically, the work will identify the neural mechanism(s) underlying modulation of multisensory prey capture by the stress neuropeptide corticotropin-releasing factor (CRF). In the clawed frog, Xenopus laevis, CRF rapidly inhibits prey capture through modulation within the optic tectum, an important brain area for multisensory processing of both prey and predator cues in this and other vertebrates. The PI will now determine if tectal CRF R1 receptors inhibit multisensory guided prey capture. In the first aim, pharmacological and imaging approaches will be used to test if tectal CRF R1 receptors interfere with the processing of lateral line and/or visual cues related to prey capture. In the second aim, the role of sensory afferents and inhibitory GABA+ interneurons in mediating CRF inhibition of multisensory guided prey capture will be investigated. Together, these experiments will identify the mechanisms through which an important satiety peptide interferes with a multisensory pathway required for food acquisition. The findings will broadly impact our understanding of the neuronal basis for aversive behavior and its modulation in vertebrates and possibly shed light on the evolutionary origins of disorders in which fear processing pathways are disrupted. Work associated with this proposal will also be directly incorporated into undergraduate educational experiences, in the classroom and the laboratory, and will guide the development of exhibits in the local community.