CAREER: Understanding the persistent effects of the food environment on taste sensation

像创伤和虐待这样的生活经历会对大脑产生持久的影响，改变动物一生的行为。这是因为事件的记忆被写入并持续存在，而不受环境变化的影响。这些记忆限制了对未来刺激的可能行为反应的范围，并可能将动物锁定在不适应的行为模式中。这些记忆是如何被记录下来的，它们是如何影响行为的，以及它们是如何在大脑中蚀刻的，这些都很难研究。在这里，研究人员将实施一个研究和教育平台，以了解饮食环境对大脑的持久影响。具体来说，他们将使用遗传易感的模式生物果蝇（果蝇）来研究社会中普遍存在的高糖饮食如何永久性地改变味觉和摄食行为。广泛影响的目标是建立一个外联平台，传播关于环境影响对大脑的持久影响的准确和可获得的知识。该平台的目标受众是各个年龄段的人，挑战传统的校园界限。总之，这个项目的学术影响和更广泛的影响，通过揭示和传播环境，特别是饮食，对大脑和行为产生持久影响的机制，对公共卫生领域产生了影响。饮食组成改变了感觉信息的外围处理，而这反过来又影响了食物选择和食物摄入量。首席研究员最近表明，高糖饮食降低了d.m anogaster的感觉神经元对甜味的反应。此外，研究人员还建立了甜味变化与己糖胺生物合成途径（HPB）作用之间的因果关系，这是一种由高水平糖激活的代谢信号通路。初步实验表明，HPB需要多梳抑制复合体2 （Polycomb suppression Complex 2, PRC2）的基因沉默活性来降低甜味，这为食物环境与行为之间的联系提供了一种机制。该项目通过(1)确定PRC2操作对甜感觉神经元活动的影响，揭示了PRC2导致甜感觉细胞生理持续变化的分子机制；(2)确定PRC2靶点如何影响感觉神经元的生理功能，从而降低甜味功能；(3)确定甜味缺陷是如何在高糖环境中持续存在的。这些目标是通过基因、分子和行为方法的结合来实现的。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Life experiences like trauma and abuse can have lasting effects on the brain, altering the behavior of animals for a lifetime. This occurs because a memory of the event is written and persists beyond the environmental circumstances' change. These memories limit the range of possible behavioral responses to future stimuli and may lock animals into maladaptive patterns of behavior. How these memories are written, how they influence behaviors, and how they become etched in the brain has been hard to study. Here the investigators will implement a research and educational platform to understand the enduring effects of the dietary environment on the brain. Specifically, they will use the genetically tractable model organism Drosophila melanogaster (fruit fly) to study how high dietary sugar, which is prevalent in society, permanently changes taste sensation and feeding behavior. The broad impact goal is to develop an outreach platform to disseminate accurate and accessible knowledge on the lasting effects of environmental influences on the brain. The target audience of that platform are people of all ages and challenges traditional campus boundaries. Together, the intellectual and the broader impact this project have implications for the field of public health by uncovering and communicating the mechanisms through which the environment, and especially diet, has a lasting effect on brain and behavior. Diet composition alters the peripheral processing of sensory information, and this, in turn, influences food choice and food intake. The principal investigator recently showed that high dietary sugar decreases the responses of the sensory neurons to sweetness in D. melanogaster. Furthermore, the investigator established a causal link between changes in sweet sensation to the action of the Hexosamine Biosynthesis Pathway (HPB), a metabolic signaling pathway activated by high levels of sugar. Preliminary experiments show that the HPB requires the gene silencing activity of the Polycomb Repressive Complex 2 (PRC2) to decrease sweet taste, which provides a mechanism to link food environment and behavior. This project uncovers the molecular mechanisms through which PRC2 leads to persistent changes in the physiology of the sweet sensing cells by (1) determining the effect of PRC2 manipulations on the activity of the sweet sensing neurons; (2) establishing how PRC2 targets affect the physiology of the sensory neurons to decrease sweet taste function; and (3) identifying how sweet taste deficits persist beyond exposure to the high sugar environment. These aims are pursued using a combination of genetic, molecular, and behavioral approaches.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.