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

描述(由申请人提供)：刺激性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有很大争议的问题。对潜在食物来源的评估为解决大脑中的价值表征提供了一个便利的框架，因为它在自然界中无处不在。此外，随着全球人口面临肥胖率和与肥胖症相关的严重疾病的激增，了解管理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，对于接近什么食物来源都非常敏锐，即使在多种可行的选择中进行选择时也是如此，气味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。大脑如何代表复杂的刺激，在这种情况下是气味，以便对环境线索产生适当的行为？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，神经系统相对容易控制，而且有丰富的遗传工具可用于观察和操纵目标神经种群。我们将首先确定果蝇对不同食物的偏爱行为。然后，我们将使用体内双光子钙成像，用单细胞分辨率检查观察到的食物气味值与嗅觉和神经调节神经群体目标亚群中的活动之间的关系。我们特别感兴趣的是果蝇神经肽F神经元的作用，它是哺乳动物食欲素神经肽Y的功能同源物，它是与食物相关的食欲行为的重要调节因素。然后，我们将对这些种群中的神经活动进行遗传操作，包括长期和剧烈的，以改变 行为偏好，确立必要性和充分性。一旦建立了关键的神经细胞亚群，我们将使用光激活和免疫染色相结合的方法绘制这些神经元的连接性图，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。综上所述，这些实验的目的是描述一种特定类别的刺激--食物气味--的价值是如何在大脑中灵活表达的，并描绘出这种灵活行为的神经回路。我们的建议是 识别中央大脑计算食物气味值的方式和电路不仅有助于我们理解大脑如何组织与食物相关的信息，而且最终将如何将感觉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.