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可能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且在环境环境变化之后保持不变。这些记忆限制了对未来刺激可能做出的行为反应的范围，并可能将动物锁定在不适应的行为模式中。这些记忆是如何书写的，它们是如何影响行为的，它们是如何在大脑中铭刻下来的，一直很难研究。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。具体地说，他们将使用遗传易驯化的模式生物黑腹果蝇(果蝇)来研究在社会上普遍存在的高饮食糖如何永久性地改变味觉和进食行为。广泛的影响目标是开发一个外联平台，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，并挑战传统的校园边界。通过揭示和沟通环境，尤其是饮食对大脑和行为产生持久影响的机制，该项目的智力和更广泛的影响共同对公共卫生领域产生了影响。饮食结构改变了感官信息的外围处理，进而影响食物的选择和摄入量。首席研究人员最近发现，高糖饮食会降低黑腹金丝猴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)之间的因果联系，己糖胺生物合成途径是一种由高糖激活的代谢信号途径。初步实验表明，HPB需要多梳抑制复合体2(PRC2)的基因沉默活性来降低甜味，这提供了一种将食物环境和行为联系起来的机制。该项目通过以下几个方面揭示了PRC2导致甜味感觉细胞生理持续变化的分子机制：(1)确定PRC2操作对甜味感觉神经元活动的影响；(2)确定PRC2靶标如何影响感觉神经元的生理从而降低甜味功能；以及(3)确定甜味缺陷如何在暴露于高糖环境后持续存在。这些目标是通过基因、分子和行为方法的组合来实现的。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.