Neural circuits that mediate computation of salience

项目摘要/摘要 神经系统的一个基本功能是确定环境中感觉刺激的突出程度。 并相应地调节对它们的注意反应。显著程度是动态的。对于动物来说，什么是突出的 随时随地变化，符合其经验和当前的生理需要。素数 在各种物种中广泛观察到的例子是与食物相关的刺激的显著程度。这些刺激物对 这些动物缺乏食物，因此需要它们的关注。相比之下，与食物相关的刺激失去了 当动物变得饱足时的凸起。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。根据当前需求和需求适当确定重点 因此，调节注意力对于生存是必不可少的，而注意力调节失调与神经精神疾病有关 精神错乱。然而，目前还不知道是什么神经回路调节了注意行为，以及这些回路是如何调节注意行为的 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来解剖 控制对食物相关嗅觉刺激的注意行为的神经回路与饥饿和 饱腹感。我们采用了一种多学科方法，结合了一种新的行为分析、一种新的双向 神经活动报告器，遗传和光遗传操作，以及体内记录神经活动以进行测试 我们的假设是，一个受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著程度。在目标1中，我们将 确定食物气味的突出程度受饥饿状态的调节，并将决定蘑菇的作用 身体对嗅觉刺激产生注意反应。在目标2中，我们将确定对饥饿敏感 多巴胺神经元，其活动受到反映饥饿和饱腹感的信号的调节。在《目标3》中，我们将 识别整合了食物气味和饥饿状态信息的蘑菇身体输出，以驱动注意力 行为。我们的研究将共同揭示大脑中调节注意行为的神经机制 对食物相关气味的反应与饥饿状态一致。果蝇的功能组织 蘑菇体与哺乳动物的纹状体及其多巴胺输入有显著的相似之处，并且 长期以来，哺乳动物体内的多巴胺回路一直被认为与显著度的计算有关。因此，我们预计 我们的项目将有助于提供对神经回路工作原理的理解 调解显著程度的确定。

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.