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

总结 多感觉整合是大脑的一项基本功能， 不同的感觉形式被组合以形成统一的感知。多感觉整合的缺陷可以 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 在健康和患病的大脑中起着重要作用，目前还不清楚多感觉整合是如何在大脑中发挥作用的。 在大脑中，在神经元网络的水平上实现。我们知识上的这种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研究的，在那里很难 了解神经元活动模式如何从特定的连接结构中出现。 在这个建议中，我们提出了一个计划，研究多感觉的基本机制， 整合使用果蝇蘑菇体作为模型系统。蘑菇体主要是 但最近的研究，包括我们自己的初步数据表明， 也是多感官整合的场所在这个提议中检验的中心假设是， 身体通过两种不同的机制整合感官信息：一种是附加机制， 单个蘑菇体神经元只接受来自一个感觉系统和一个整合系统的输入。 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 通过初步分析，我们已经确定了从不同感觉中枢投射的神经元，包括 视觉，嗅觉，味觉，温度和湿度的感觉中心-蘑菇体。我们 提出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 蘑菇体神经元连接到不同的感觉系统使用神经元追踪技术， 已经发展。第二，我们将确定整个蘑菇体神经元群体如何响应 多感官刺激使用钙成像。第三，我们将确定是否，当学习复杂 在多感官刺激下，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，功能和行为证据支持我们的研究。 假说.该提案一旦完成，将确定连通性的基本机制， 蘑菇体中多感觉整合的潜在功能。鉴于许多基本设计 感觉系统的原则在无脊椎动物和脊椎动物之间是保守的，很可能是 果蝇多感觉整合的连接和功能机制也将被 在更复杂的哺乳动物大脑中是保守的。我们研究计划的首要目标是应用 我们的研究结果更广泛的背景下：我们相信，通过更好地理解数字简单 果蝇蘑菇体整合、表征和转换多感官信息，我们将获得洞察力 这些机制如何在人类大脑中实现，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.