Neural circuits that mediate computation of salience

项目总结/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著性 并相应地调节对它们的注意力反应。突出是动态的。对动物来说， 根据自身的经验和当前的生理需要，每时每刻都在发生雅阁。一个主要 在物种中广泛观察到的一个例子是食物相关刺激的显著性。这些刺激对于 食物匮乏的动物，因此需要他们的关注。相比之下，与食物相关的刺激失去了它们的 当动物变得满足时的显著性。这表明控制注意力行为的神经回路 整合了饥饿和饱足的信息。根据当前需要适当确定突出性， 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 紊乱然而，目前还不知道是什么神经回路介导注意力行为，以及这些回路如何调节注意力行为。 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， 控制注意行为的神经回路与食物相关的嗅觉刺激雅阁饥饿和 饱腹感我们采用了一种多学科的方法，结合了一种新的行为测定，一种新的双向 神经活性报告基因、遗传学和光遗传学操作以及体内记录神经活性以测试 我们的假设是，多巴胺调节的嗅觉中心，蘑菇体，在 基于当前饥饿状态适当地计算食物相关气味的显著性。在目标1中，我们 确定食物气味的显著性受饥饿状态的调节，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 多巴胺神经元，其活动由反映饥饿和饱腹感的信号调节。在目标3中，我们 识别整合食物气味和饥饿状态信息以驱动注意力的蘑菇体输出 行为总之，我们的研究将揭示调节注意力行为的神经机制， 对食物相关气味的反应符合饥饿状态的雅阁。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具有显著的相似性， 哺乳动物的多巴胺回路长期以来一直与计算显著性有关。因此我们预计 我们的项目将有助于理解神经回路的运作原理， 介导显著性确定。

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.