The role of the dNPF brain circuit in coding food odor value

描述（由申请人提供）：刺激估值是决定我们如何与世界联系的关键一步。然而，大脑计算和表示价值的方式仍然是一个备受争议的问题。潜在的食物来源的评估提供了一个权宜的框架，以解决在大脑中的价值表征，因为它在自然界中无处不在。此外，随着全球人口面临肥胖和与肥胖相关的严重医疗状况的患病率的压倒性上升，了解食物选择和偏好的过程对人类健康至关重要。 在正常情况下，大多数动物，包括果蝇，对接近什么样的食物来源非常挑剔，即使在多个可行的选择和气味之间进行选择是所有动物用来跟踪，评估和选择可用食物的最重要的感官线索之一。大脑如何表征复杂的刺激，在这种情况下，气味，以产生适当的行为，以环境线索？果蝇是一种无与伦比的模式生物，可以用来研究这些问题，因为它们的行为复杂，神经系统相对容易处理，并且有丰富的遗传工具可以用来观察和操纵目标神经群体。 我们首先从行为学上建立果蝇对不同食物的反应。然后，我们将检查与单细胞分辨率，使用体内双光子钙成像，观察到的食物气味值和活性之间的关系，在目标子集的嗅觉和神经调节神经种群。我们特别感兴趣的是果蝇神经肽F神经元的作用，哺乳动物食欲神经肽Y的功能同系物，这是一个突出的调节食物相关的食欲行为。然后，我们将从基因上操纵这些人群的神经活动，包括慢性和急性， 行为偏好，建立必要性和充分性。一旦建立了关键的神经子集，我们将使用光活化和免疫染色的组合来绘制这些神经元的连接，然后通过遗传操作和功能成像来确定下游靶点的功能特征。 总之，这些实验的目的是描述一类特定的刺激，食物气味的价值，是如何灵活地在大脑中表现出来的，并描绘出这种灵活行为的神经回路。我们建议 确定中央大脑计算食物气味值的方式和电路不仅会让我们了解大脑如何组织传入的食物相关信息，而且最终会让我们了解大脑如何将感官输入转化为行为反应。

DESCRIPTION (provided by applicant): Stimulus valuation is a critical step in determining how we relate with the world. Yet the way the brain computes and represents value remains a matter of much debate. The assessment of potential food sources provides an expedient framework to address value representation in the brain given its ubiquity in nature. Moreover, with the global population facing overwhelming rises in the prevalence of obesity and obesity-related serious medical conditions, the need for understanding the processes governing food selection and preferences has become of paramount importance to human health. Under normal conditions most animals, including Drosophila, are extremely discerning about what food sources to approach, even when given the choice between multiple viable options and odors are one of the most important sensory cues all animals use to track, evaluate and select among available foods. How does the brain represent complex stimuli, in this case odorants, in order to generate appropriate behaviors to environmental cues? Drosophila are an unparalleled model organism with which to study such questions given their complex behavior, relatively tractable nervous system, and the wealth of genetic tools available to both observe and manipulate targeted neural populations. We will first establish Drosophila's partiality for differing food odrs behaviorally. We will then examine with single-cell resolution, using in vivo two-photon calcium imaging, the relationship between observed food- odor values and activity in targeted subsets of olfactory and neuromodulatory neural populations. We are specifically interested in the role of Drosophila Neuropeptide F neurons, the functional homolog of mammalian orexigenic Neuropeptide Y which is a prominent regulator of food-related appetitive behaviors. We will then genetically manipulate neural activity in these populations, both chronically and acutely, to alter behavioral preferences, establishing necessity and sufficiency. Once critical neural subsets are established we will map the connectivity of these neurons using a combination of photoactivation and immunostaining and then determine the functional characteristics of downstream targets through both genetic manipulation and functional imaging. Taken together, these experiments aim to describe how value of a specific class of stimuli, food odor, is flexibly represented in the brain and delineate a neural circuit for such flexible behavior. Our proposal to identify the manner and circuits by which the central brain computes food-odor value will not only inform our understanding of how the brain organizes incoming food-related information but ultimately how the brain translates sensory input into behavioral responses.