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.

项目摘要 /摘要 神经系统的基本功能是确定环境中感觉刺激的显着性 因此，调节对他们的注意力反应。显着性是动态的。什么是动物的重要性 一时的变化符合其经验和当前的生理需求。素数 在物种之间广泛观察到的例子是食物相关刺激的显着性。这些刺激是显着的 食物不足的动物，因此需要他们的注意。相比之下，食物相关的刺激失去了 当动物满足时的显着性。这表明控制注意行为的神经回路 整合了饥饿和饱腹感的信息。根据当前需求和 因此，调节注意力对于生存至关重要，其失调与神经精神病学有关 疾病。但是，尚不知道哪些神经回路介导了注意行为以及这些电路如何 整合饥饿和饱腹感的内部信息。在这里，我们建议使用果蝇作为模型进行剖析 根据饥饿和饥饿和 饱腹感。我们采用多学科方法，结合了一种新型的行为分析，这是一种新型的双向 神经活动记者，遗传和光遗传操作以及在体内记录神经活动以测试 我们假设多巴胺调节的嗅觉中心蘑菇体在 基于当前的饥饿状态，适当地计算出与食物相关的气味的显着性。在AIM 1中，我们将 确定食物气味的显着性是由饥饿状态调节的，并将确定蘑菇的作用 身体对嗅觉刺激产生注意力反应的身体。在AIM 2中，我们将确定对饥饿敏感的 多巴胺神经元，其活性是由反映饥饿和饱腹感的信号调节的。在AIM 3中，我们将 识别蘑菇体产量，集成食物气味和饥饿状态以吸引注意力 行为。我们的研究将共同​​揭示调节注意行为的神经机制 根据饥饿状态对食物相关气味的反应。果蝇的功能组织 蘑菇体表现出与哺乳动物纹状体及其多巴胺输入的相似之处，并且 长期以来，哺乳动物中的多巴胺回路与显着性计算有关。因此，我们期望 我们的项目将有助于提供对神经回路的操作原理的理解 调解显着性的确定。