Neural circuits that mediate computation of salience

介导显着性计算的神经回路

• 批准号: 10599214
• 负责人: Daisuke Hattori
• 金额: $ 45.57万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10599214
• 关键词: Acute; Affect; Animals; Appearance; Architecture; Association Learning; Attention; Behavior; Behavioral; Behavioral Assay; Brain; Corpus striatum structure; Cues; Data; Dopamine; Drosophila genus; Eating Disorders; Environment; Exhibits; Food; Food deprivation (experimental); Foundations; Functional disorder; Genetic; Goals; Hunger; Mammals; Mediating; Modeling; Mushroom Bodies; Nervous System Physiology; Neurons; Odors; Output; Physiological; Play; Process; Reporter; Role; Satiation; Sensory; Signal Transduction; Stimulus; Substance Use Disorder; Testing; Therapeutic Intervention; analog; attentional control; attentional modulation; directed attention; dopamine system; dopaminergic neuron; experience; experimental study; flexibility; fly; genetic manipulation; in vivo; in vivo calcium imaging; interdisciplinary approach; neural; neural circuit; neuromechanism; neuropsychiatric disorder; novel; olfactory stimulus; optogenetics; ratiometric; response; sensory stimulus; transcriptomics

PROJECT SUMMARY / ABSTRACT A fundamental function of the nervous system is to determine salience of sensory stimuli in the environment and accordingly regulate attentional response to them. Salience is dynamic. What is salient to an animal changes from moment to moment in accord with its experience and current physiological need. A prime example observed widely across species is the salience of food-associated stimuli. These stimuli are salient for food-deprived animals and therefore demand their attention. By contrast, food-associated stimuli lose their salience when animals become satiated. This indicates that neural circuits that control attentional behavior integrates the information of hunger and satiety. Appropriately determining salience based on current need and thereby regulating attention is essential for survival and its dysregulation is associated with neuropsychiatric disorders. However, it is not known what neural circuits mediate attentional behavior and how these circuits integrate internal information of hunger and satiety. Here we propose to use Drosophila as a model to dissect neural circuits that control attentional behavior to food-associated olfactory stimuli in accord with hunger and satiety. We employ a multidisciplinary approach that combines a novel behavioral assay, a novel bidirectional neural activity reporter, genetic and optogenetic manipulations, and in vivo recording of neural activity to test our hypothesis that a dopamine-modulated olfactory center, the mushroom body, plays a key role in appropriately computing salience of food-associated odors based on current hunger state. In Aim 1, we will establish that the salience of food odor is modulated by hunger state and will determine the role of mushroom body in generating attentional response to olfactory stimuli. In Aim 2, we will identify hunger-sensitive dopamine neurons, whose activity is modulated by signals reflecting hunger and satiety. In Aim 3, we will identify mushroom body output that integrates information of food odors and hunger state to drive attentional behavior. Together, our studies will reveal the neural mechanisms that regulate attentional behavior in response to food-associated odors in accord with hunger state. The functional organization of the Drosophila mushroom body exhibits remarkable similarity to that of the mammalian striatum and its dopamine input, and the dopamine circuits in mammals have long been implicated in computation of salience. Therefore, we expect that our project will contribute to providing an understanding of the operational principles of neural circuits that mediate salience determination.

项目概要/摘要 神经系统的一个基本功能是确定环境中感觉刺激的显着性 并相应地调节对它们的注意力反应。显着性是动态的。对于动物来说什么最重要 根据其经验和当前的生理需要而随时变化。素数 在各个物种中广泛观察到的一个例子是与食物相关的刺激的显着性。这些刺激对于 缺乏食物的动物因此需要他们的关注。相比之下，与食物相关的刺激就失去了作用 当动物吃饱时，这种现象会更加明显。这表明控制注意力行为的神经回路 整合饥饿和饱足信息。根据当前需求和情况适当确定显着性 因此，调节注意力对于生存至关重要，其失调与神经精神相关 失调。然而，目前尚不清楚什么神经回路介导注意力行为以及这些回路如何介导注意力行为。 整合饥饿和饱腹感的内部信息。这里我们建议使用果蝇作为模型来解剖 根据饥饿和饥饿控制对与食物相关的嗅觉刺激的注意力行为的神经回路 饱腹感。我们采用多学科方法，结合新颖的行为分析、新颖的双向 神经活动报告器、遗传和光遗传学操作以及神经活动的体内记录以进行测试 我们的假设是，多巴胺调节的嗅觉中枢，即蘑菇体，在 根据当前饥饿状态适当计算与食物相关的气味的显着性。在目标 1 中，我们将 确定食物气味的显着程度受饥饿状态调节，并将决定蘑菇的作用 身体对嗅觉刺激产生注意力反应。在目标 2 中，我们将确定饥饿敏感人群 多巴胺神经元，其活动受到反映饥饿和饱腹感的信号调节。在目标 3 中，我们将 识别蘑菇体输出，整合食物气味和饥饿状态信息以引起注意 行为。我们的研究将共同​​揭示调节注意力行为的神经机制 根据饥饿状态对与食物相关的气味做出反应。果蝇的功能组织 蘑菇体与哺乳动物纹状体及其多巴胺输入表现出显着的相似性，并且 哺乳动物的多巴胺回路长期以来一直与显着性的计算有关。因此，我们期望 我们的项目将有助于理解神经回路的运作原理 中介显着性确定。