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

摘要 多感官整合是大脑的一项基本功能，通过这种功能收集的信息 不同的感觉形式结合在一起形成一个统一的知觉。多感官整合的缺陷可能 影响知觉，是包括自闭症谱系障碍在内的许多精神疾病的标志。尽管它的 在健康和患病的大脑中起着重要作用，但目前尚不清楚多感觉整合是如何 在大脑中实施，在神经元网络的水平上。我们知识上的这种鸿沟很大程度上源于 事实上，多感觉整合主要是在灵长类动物的大脑中研究的，在那里很难 了解神经元活动模式是如何从特定的连接架构中出现的。 在这项提案中，我们提出了一个研究多感官基本机制的计划 以果蝇蘑菇体为模型系统进行集成。蘑菇体主要是 被研究为嗅觉大脑中心，但最近的研究，包括我们自己的初步数据，表明它 也是多感官整合的场所。在这项提议中检验的中心假设是蘑菇 身体通过两种不同的机制整合感觉信息：一种相加机制，借此 单个蘑菇体神经元仅从一个感觉系统和一个整合的 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，我们已经确定了从不同感觉中心投射的神经元-包括 从视觉、嗅觉、味觉、温觉和湿感中枢--到蘑菇体。我们是 提出通过追求三个具体目标来检验我们的领先假说。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对 使用钙质成像的多感官刺激。第三，我们会确定，在学习复杂的时候 多感官刺激，果蝇学习这些刺激的个体特征。 总之，这三个目标将提供解剖学、功能和行为方面的证据，支持我们的 假设。一旦完成，这项提案将勾勒出互联互通和 蘑菇体内多感官整合的潜在功能。考虑到许多基本设计 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 果蝇多感官整合的连接和功能机制也将是 保存在更复杂的哺乳动物大脑中。我们研究计划的首要目标是应用 我们的发现延伸到更广泛的背景下：我们认为，通过更好地理解数字如何简单 果蝇蘑菇体集成、表达和转换多感官信息，我们将获得洞察力 这些机制是如何在人脑中实现的，以及它们的功能障碍如何导致缺陷 在感知上。

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.