The mechanisms of connectivity and function underlying multisensory integration in the Drosophila melanogaster mushroom body

果蝇蘑菇体内多感觉整合的连接和功能机制

• 批准号: 10204131
• 负责人: Sophie Caron
• 金额: $ 33.36万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10204131
• 关键词: Adverse effects; Affect; Anatomy; Architecture; Behavioral; Behavioral Paradigm; Biological Models; Blueberries; Brain; Brain Diseases; Brain region; Calcium; Cells; Color; Complex; Cues; Data; Defect; Drosophila genus; Drosophila melanogaster; Esters; Fruit; Functional disorder; Goals; Human; Image; Individual; Interneurons; Invertebrates; Knowledge; Lead; Learning; Maps; Mediating; Memory; Mental disorders; Modality; Modeling; Mushroom Bodies; Neurons; Odors; Outcome; Output; Patients; Pattern; Perception; Peripheral; Population; Primates; Process; Property; Research; Research Proposals; Role; Sensory; Shapes; Site; Smell Perception; Stimulus; Structure; System; Techniques; Testing; Vertebrates; Visual; Work; autism spectrum disorder; classical conditioning; design; experimental study; fly; insight; multimodality; multisensory; piriform cortex; programs; response; sensory system; stem; therapy development; visual information

SUMMARY Multisensory integration is a fundamental function of the brain whereby the information collected through different sensory modalities is combined to form a unified percept. Defects in multisensory integration can affect perception and are a hallmark of many mental illnesses including autism spectrum disorders. Despite its fundamental role in the healthy and diseased brain, it remains unclear how multisensory integration is implemented in the brain, at the level of neuronal networks. This gap in our knowledge stems largely from the fact that multisensory integration has been primarily studied in the primate brain, where it is difficult to understand how neuronal activity patterns emerge from a specific connectivity architecture. In this proposal, we are putting forward a plan to investigate the basic mechanisms of multisensory integration using the Drosophila mushroom body as a model system. The mushroom body has been primarily investigated as an olfactory brain center but recent studies, including our own preliminary data, suggest that it is also a site for multisensory integration. The central hypothesis tested in this proposal is that the mushroom body integrates sensory information through two different mechanisms: an additive mechanism, whereby individual mushroom body neurons receive input only from only one sensory system and an integrative mechanism whereby individual mushroom body neurons integrate input from multiple sensory systems. In our preliminary analyses, we have identified the neurons projecting from different sensory centers — including visual, olfactory, gustatory, thermosensory and hygrosensory centers — to the mushroom body. We are proposing to test our leading hypothesis by pursuing three specific aims. First, we will determine how individual mushroom body neurons are connected to different sensory systems using a neuronal tracing technique we have developed. Second, we will determine how the entire population of mushroom body neurons responds to multisensory stimuli using calcium imaging. Third, we will determine whether, when learning complex multisensory stimuli, Drosophila learns individual features of these stimuli. Altogether, these three aims will provide anatomical, functional and behavioral evidence supporting our hypothesis. Once completed, this proposal will have delineated the basic mechanisms of connectivity and function underlying multisensory integration in the mushroom body. Given that many fundamental design principles of sensory systems are conserved between invertebrates and vertebrates, it is likely that the mechanisms of connectivity and function underlying multisensory integration in Drosophila will too be conserved in the more complex mammalian brain. The overarching goal of our research program is to apply our findings to a broader context: we believe that by understanding better how the numerically simple Drosophila mushroom body integrates, represents and transforms multisensory information, we will gain insight into how these mechanisms are implemented in the human brain and how their dysfunction can lead to defects in perception.

概括 多感觉整合是大脑的一项基本功能，通过它收集的信息 不同的感觉方式结合起来形成统一的知觉。多感觉统合缺陷 影响感知，是包括自闭症谱系障碍在内的许多精神疾病的标志。尽管其 尽管多感觉整合在健康和患病大脑中发挥着重要作用，但目前尚不清楚它是如何发挥作用的 在大脑的神经元网络层面上实施。我们知识上的差距很大程度上源于 事实上，多感觉整合主要是在灵长类动物的大脑中进行研究的，而在灵长类动物的大脑中很难 了解神经元活动模式如何从特定的连接架构中产生。 在这个提案中，我们提出了一个计划来研究多感官的基本机制 使用果蝇蘑菇体作为模型系统进行整合。蘑菇体主要是 作为嗅觉大脑中枢进行了研究，但最近的研究，包括我们自己的初步数据，表明它 也是一个多感官整合的网站。该提案检验的中心假设是蘑菇 身体通过两种不同的机制整合感官信息：附加机制，其中 单个蘑菇体神经元仅接收来自一个感觉系统和一个综合系统的输入 单个蘑菇体神经元整合来自多个感觉系统的输入的机制。在我们的 初步分析，我们已经识别出从不同感觉中心投射的神经元——包括 视觉、嗅觉、味觉、热觉和湿度感觉中心——到蘑菇体。我们是 提议通过追求三个具体目标来检验我们的主要假设。首先，我们将确定个人如何 我们使用神经元追踪技术将蘑菇体神经元连接到不同的感觉系统 已经发展起来了。其次，我们将确定整个蘑菇体神经元群体如何响应 使用钙成像的多感觉刺激。第三，我们将确定学习时是否复杂 多感官刺激，果蝇学习这些刺激的个体特征。 总而言之，这三个目标将提供支持我们的解剖学、功能和行为证据 假设。一旦完成，该提案将勾勒出互联互通和互联互通的基本机制。 蘑菇体内多感觉整合的功能。鉴于许多基本设计 感觉系统的原理在无脊椎动物和脊椎动物之间是保守的，很可能 果蝇多感觉整合的连接和功能机制也将被 保存在更复杂的哺乳动物大脑中。我们研究计划的总体目标是应用 我们的发现适用于更广泛的背景：我们相信，通过更好地理解数字上简单的 果蝇蘑菇体整合、表征和转化多感官信息，我们将获得洞察 研究这些机制如何在人脑中实施以及它们的功能障碍如何导致缺陷 在感知中。