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: 10468042
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10468042
• 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础功能。 将不同的感觉模态组合在一起以形成统一的感知。 影响感知，是许多精神精神疾病的标志，包括自闭症谱系障碍 在健康和患病的大脑中的基本作用，尚不清楚多感觉整合如何IST 在大脑中，在我们的知识中，这一差距很大程度上源于您 多感觉整合在灵长类动物的大脑中进行了初步研究 了解神经元活动模式如何从特定的连接体系结构中出现。 在此提案中，我们提出了多义的基本机制 使用果蝇蘑菇体作为模型系统的整合。 被调查为嗅觉脑中心，但最近的研究，包括我们自己的预启示数据，表明它是ITIGHT 也用于多感官整合。 身体通过两种不同的机制整合了感官信息：一种加性机制 单个蘑菇体神经元仅收到输入一个感官系统和一个集成 单个蘑菇身体神经元的机制使输入一些 初步分析，我们从不同的感觉中心确定了神经元项目，包括 视觉，嗅觉，味道，热体和湿气中心 - 我们是蘑菇体 通过追求三个特定目标来检验我们的主要假设。 蘑菇体神经元使用神经元技术连接到不同的感觉系统 第二 使用钙成像的多感官刺激。 多感官刺激，果蝇学习了刺激的单个特征。 总之，三个目标将提供解剖，功能和行为证据，以支持我们 曾经的假设。 蘑菇体中多感官整合的功能。 感觉系统的原理是无脊椎动物和脊椎动物之间的保守的，您可能很可能 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Mamalian大脑中保守的是我们研究计划的总体目标 我们在更广泛的背景下的发现：我们相信数字简单 果蝇蘑菇体整合，代表和转换多感官信息，我们将获得洞察力 涉及如何在人脑中实现机制以及功能障碍如何导致缺陷 在感知中。