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

dNPF 脑回路在编码食物气味值中的作用

• 批准号: 9199222
• 负责人: JOSHUA T DUBNAU
• 金额: $ 33.68万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9199222
• 关键词: Acute; Address; Anatomy; Animal Model; Animals; Appetite Stimulants; Appetitive Behavior; Behavior; Behavioral; Biological Assay; Brain; Categories; Cells; Characteristics; Chronic; Code; Complex; Cues; Data; Desire for food; Drosophila genus; Drosophila neuropeptide F; Environment; Food; Food Preferences; Food Selections; Functional Imaging; Genetic; Health; Health Care Costs; Homologous Gene; Human; Image; Income; Individual; Invertebrates; Maps; Medical; Monitor; Mushroom Bodies; Nature; Nervous system structure; Neurons; Neurosciences; Obesity; Odors; Olfactory Pathways; Pattern; Population; Positioning Attribute; Prevalence; Process; Property; Public Health; Research Infrastructure; Resolution; Role; Satiation; Sensory; Series; Site; Source; Specificity; Starvation; Stimulus; Structure; System; Translating; United States; Vertebrates; behavioral response; experimental study; flexibility; fly; genetic approach; genetic manipulation; hedonic; imaging approach; in vivo; in vivo calcium imaging; in vivo two-photon imaging; insight; interest; knock-down; neural circuit; neuropeptide Y; neuroregulation; olfactory stimulus; photoactivation; preference; public health relevance; receptor; relating to nervous system; response; sensory input; sensory stimulus; stem; tool; two-photon

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.

描述（由申请人提供）：刺激评估是确定我们如何与世界建立联系的关键步骤。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。鉴于大脑在自然界中普遍存在，对潜在食物来源的评估提供了一个解决大脑中价值表征的权宜框架。此外，随着全球人口面临肥胖和与肥胖相关的严重疾病患病率急剧上升的情况，了解控制食物选择和偏好的过程对人类健康变得至关重要。 在正常情况下，包括果蝇在内的大多数动物对接近的食物来源都非常有洞察力，即使在多种可行的选择之间进行选择，气味也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。大脑如何表示复杂的刺激（在本例中为气味剂），以便根据环境线索产生适当的行为？果蝇是一种无与伦比的模型生物体，由于其复杂的行为、相对容易处理的神经系统以及可用于观察和操纵目标神经群体的丰富的遗传工具，因此可以用它来研究这些问题。 我们首先从行为上确定果蝇对不同食物气味的偏好。然后，我们将使用体内双光子钙成像，以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目标亚群的活动之间的关系。我们对果蝇神经肽 F 神经元的作用特别感兴趣，它是哺乳动物食欲神经肽 Y 的功能同源物，是食物相关食欲行为的重要调节剂。然后，我们将对这些人群的神经活动进行长期和急性的基因操纵，以改变 行为偏好，确定必要性和充分性。一旦建立了关键的神经子集，我们将结合光激活和免疫染色来绘制这些神经元的连接图，然后通过基因操作和功能成像来确定下游靶标的功能特征。 总而言之，这些实验旨在描述特定类别的刺激（食物气味）的价值如何在大脑中灵活地表达，并描绘出这种灵活行为的神经回路。我们的建议是 确定中枢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传入的食物相关信息，而且最终有助于我们理解大脑如何将感官输入转化为行为反应。