Harnessing sensory food circuits to influence feeding behavior

项目总结 我们的现代食物环境，以及它广泛可获得的高能量、美味的食物和相关的 线索，被认为与我们的生理相互作用，以促进食物的摄取。这也是造成这一急剧增长的原因。 在过去的几十年里，美国的肥胖率有所下降。然而，大多数药理减肥 策略针对的是饱腹感途径，而不是感官途径，因此在消除 环境/感官暗示对食物摄入量的影响。在这里，我们建议采取一种新的方法来 通过检查感官和营养食物信号的神经整合来理解进食的动力。第一, 我们将创建感觉“印记”--由离散的感觉刺激激活的神经元的功能图--以及 确定激活或抑制这些回路如何影响人们对食物的偏好。这一过程将揭示 利用“神经味觉”、“神经气味”和“神经营养”的力量--没有 外部感官输入--改变进食行为。接下来，我们将监测清醒、自由活动的神经活动 小鼠确定神经活动对食物的感官特性的反应如何与个体相关 进食行为和未来体重增加的差异。最后，我们将监测个体的钙动力学。 神经元揭示整合大脑中不同感觉和营养信息的活动模式 体重。这项提议的成功实施有可能使一条全新的 针对整合感觉和神经回路的减肥疗法的研究和开发 食物的营养特性。我在科学创新和生产力方面的记录，结合 莫内尔化学感官中心和神经科学系的协作环境 宾夕法尼亚大学，使我成为唯一适合搭建化学感觉生物学领域桥梁的人， 神经生物学和肥胖来执行这一雄心壮志的项目。总体而言，这位NIH主任的新创新者奖 将启动我早期的职业生涯，并提供智力空间来从事创新研究，这些研究可以重新定义 暴饮暴食和肥胖背后的神经机制。

PROJECT SUMMARY Our modern food environment, with its widespread availability of energy-dense, palatable foods and associated cues, is thought to interact with our physiology to promote food intake. This has contributed to the drastic increase in obesity in the United States over the past several decades. However, most pharmacological weight loss strategies target satiation pathways, not sensory pathways, and therefore may be less effective at eliminating effects of environmental/sensory cues on food intake. Here we propose to take a novel approach to understanding the drive to eat by examining the neural integration of sensory and nutritive food signals. First, we will create sensory “engrams” – functional maps of neurons activated by discrete sensory stimuli – and determine how activating or inhibiting these circuits can influence food preference. This process will reveal the power of leveraging “neural tastes,” “neural smells,” and “neural nutrients” – sensory experiences without external sensory input – to shift feeding behavior. Next, we will monitor neural activity in awake, freely moving mice to determine how neural activity in response to the sensory properties of food relates to individual differences in feeding behavior and future weight gain. Finally, we will monitor calcium dynamics in individual neurons to reveal the activity patterns that integrate sensory and nutritive information in the brain across different body weights. Successful implementation of this proposal has the potential to enable an entirely new line of research and development for weight loss therapeutics that targets neural circuits that integrate sensory and nutritive properties of food. My track record of scientific innovation and productivity, combined with the collaborative environment at the Monell Chemical Senses Center and Department of Neuroscience at the University of Pennsylvania, makes me uniquely suited to bridge the fields of chemosensory biology, feeding neurobiology, and obesity to execute a project of this ambition. Overall, this NIH Director’s New Innovator Award would launch my early career and provide the intellectual space to pursue innovative research that can redefine the neural mechanisms that underlie overeating and obesity.