Harnessing sensory food circuits to influence feeding behavior

利用感官食物回路影响进食行为

• 批准号: 10245940
• 负责人: Amber L Alhadeff
• 金额: $ 145.98万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10245940
• 关键词: Award; Biology; Body Weight; Body Weight decreased; Brain; Calcium; Chemicals; Cues; Eating; Eating Behavior; Environment; Exposure to; Feeding behaviors; Food; Food Preferences; Future; Hyperphagia; Individual; Individual Differences; Maps; Modernization; Monitor; Mus; Neurobiology; Neurons; Neurosciences; Nutrient; Obesity; Palate; Pathway interactions; Pattern; Pennsylvania; Pharmacology; Physiology; Process; Productivity; Property; Research; Satiation; Sensory; Signal Transduction; Smell Perception; Taste Perception; United States; United States National Institutes of Health; Universities; Weight Gain; awake; career; collaborative environment; experience; feeding; food environment; innovation; neural circuit; neuromechanism; novel strategies; relating to nervous system; research and development; response; sensory input; sensory integration; sensory stimulus; therapeutic target

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.

项目摘要 我们的现代食品环境，其广泛的能量密集，可口的食物和相关的 线索，被认为是与我们的生理相互作用，以促进食物的摄入。这导致了 在过去的几十年里，美国的肥胖症。然而，大多数药物减肥 策略针对饱足通路，而不是感觉通路，因此在消除 环境/感官线索对食物摄入的影响。在这里，我们建议采取一种新的方法， 通过检查感觉和营养食物信号的神经整合来理解进食的驱动力。第一、 我们将创建感觉“记忆痕迹”--由离散的感觉刺激激活的神经元的功能图-- 确定激活或抑制这些回路如何影响食物偏好。这一过程将揭示 利用“神经味觉”、“神经嗅觉”和“神经营养素”的力量--感官体验， 外部感官输入-改变进食行为。接下来，我们将监测清醒时的神经活动， 小鼠，以确定神经活动如何响应食物的感官特性与个体 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，以揭示在不同的大脑中整合感官和营养信息的活动模式。 体重成功实施这一建议有可能使一个全新的生产线， 研究和开发减肥疗法，目标是整合感觉和 食物的营养特性。我在科学创新和生产力方面的记录，加上 Monell化学感觉中心和神经科学系的协作环境 宾夕法尼亚大学，使我特别适合桥梁领域的化学传感生物学，喂养 神经生物学和肥胖来执行这个雄心勃勃的项目。总的来说，这个NIH主任的新创新者奖 我将启动我的早期职业生涯，并提供智力空间，以追求创新的研究，可以重新定义 导致暴饮暴食和肥胖的神经机制