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: 9791010
• 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/9791010
• 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 多感官整合是大脑的基本功能，通过该功能 将不同的感官方式组合在一起以形成统一的感知。多感觉集成中的缺陷可以 影响感知，并且是许多精神疾病的标志，包括自闭症谱系障碍。尽管有它 在健康和厌恶的大脑中的基本作用，尚不清楚多感官的整合 在大脑，在神经元网络的层面上实施。我们的知识步骤中的这一差距主要来自 事实，多感官整合一直是主要大脑中的主要研究 了解神经元活动模式如何从特定的连接架构中出现。 在此提案中，我们提出了一个计划，以调查多感官的基本机制 使用果蝇肌肉体作为模型系统进行整合。肌肉体一直是主要的 被调查为嗅觉脑中心，但最近的研究，包括我们自己的初步数据，表明 也是多感官集成的站点。该提议中检验的中心假设是肌肉 人体通过两种不同的机制综合感觉信息：一种加性机制，从而 单个肌肉室身体神经元仅收到仅从一个感觉系统和一个集成的输入 单个肌肉身体神经元的机制整合了来自多个感觉系统的输入。在我们的 初步分析，我们已经确定了来自不同感官中心的神经元，包括 肌肉体的视觉，嗅觉，味觉，热感和湿气中心。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 蘑菇体神经元使用神经元跟踪技术连接到不同的感觉系统 已经开发了。其次，我们将确定肌肉身体神经元的整个人群如何反应 使用钙成像的多感官刺激。第三，我们将确定学习复杂时是否 多感官刺激，果蝇学会了这些刺激的单个特征。 总之，这三个目标将提供解剖，功能和行为证据，以支持我们 假设。完成后，该提案将描述连接性的基本机制和 肌肉体内多感官整合的功能。鉴于许多基本设计 感觉系统的原理是无脊椎动物和脊椎动物之间保守的，很可能 连通性和功能的机制在果蝇中的多感官整合也将是 在更复杂的哺乳动物大脑中保守。我们研究计划的总体目标是应用 我们对更广泛的背景的发现：我们相信，通过更好地了解数值简单的方式 果蝇肌肉体的整合，代表和转换多感官信息，我们将获得洞察力 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。