Multisensory integration at the cell, circuit, and behavioral levels: How audiovisual signals drive dynamic courtship behavior in Drosophila melanogaster

细胞、回路和行为层面的多感觉整合：视听信号如何驱动果蝇的动态求偶行为

• 批准号: 10389197
• 负责人: Edna Normand
• 金额: $ 2.64万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10389197
• 关键词: Address; Animals; Attention deficit hyperactivity disorder; Auditory; Behavior; Behavioral; Biological Assay; Brain; Brain region; Calcium; Cells; Communication; Complex; Courtship; Cues; Data Set; Dementia; Disease; Doctor of Philosophy; Drosophila genus; Drosophila melanogaster; Elderly; Electron Microscopy; Environment; Facial Expression; Female; Fire - disasters; Foundations; Genetic; Gilles de la Tourette syndrome; Goals; Human; Image; Individual; Instinct; Joints; Laboratories; Left; Measurable; Methods; Modality; Modeling; Motor; Neurons; Physicians; Preparation; Process; Property; Psychoses; Reaction Time; Resolution; Role; Scientist; Sensorimotor functions; Sensory; Signal Transduction; Social Interaction; Stereotyping; Stimulus; Synapses; Testing; Time; Training; Vision; Visual; autism spectrum disorder; base; behavioral response; brain cell; career; court; deep learning; developmental disease; driving behavior; experience; falls; feature detection; fly; in vivo calcium imaging; insight; male; motor behavior; multimodality; multisensory; neural circuit; neuronal circuitry; novel; optogenetics; postsynaptic; presynaptic; programs; response; sensory processing disorder; social communication; spatiotemporal; tool; treadmill; two-photon; virtual reality

Project Summary Perceiving multisensory information and responding with appropriate, real-time behaviors is critical for normal communication and interaction with the environment. Past studies have investigated general brain regions as well as specific cells that fire in response to more than one type of sensory cue, yet have not pinpointed their presynaptic unimodal partners (inputs), meaning that the studied cells may have not been the direct points of multisensory convergence. Additionally, these neurons themselves did not then drive responsive and innate motor behavior. This has left gaps in understanding (1) how multisensory neurons acquire their multi-modal feature detection properties directly from unimodal inputs at the cellular and circuit levels, (2) how they integrate multimodal signals over time, and (3) how they then transform those signals into dynamic motor responses, all during ethologically relevant and innate interactions. Neural circuits that govern Drosophila melanogaster courtship serve as a well-developed model for sensory processing and real-time behavioral responses: during fly courtship, males sing to females, and females perceive and respond to song, which in turn alters males’ own courting behavior. This forms a complex “conversation” that emulates properties of many animals’ social interactions. Within the courtship circuit, I have discovered two direct unisensory convergence points onto multicellular cells and circuits, which have themselves been shown to be necessary and sufficient to drive and modulate robust, measurable, and innate behavior in Drosophila females, providing an unprecedented opportunity to address the gaps described above. The convergence points were identified via analysis of novel whole-brain and half-brain electron microscopy datasets at synaptic resolution. This proposal will directly elucidate principles of multisensory integration at the cellular, circuit, and behavioral levels. Through high resolution behavioral tracking assays, Aim 1 will determine how, by integrating natural combinations of audiovisual information, two multisensory neurons drive an ethologically relevant behavior in Drosophila females. Aim 2 will determine, using calcium imaging in behaving flies in a courtship virtual reality, how those neurons integrate auditory and visual signals from three of their unisensory inputs. Taken together, this study will significantly expand understanding of how brain cells and circuits process multisensory signals and transform them into dynamic motor responses, contributing to a foundation for long-term understanding of normal and disordered sensorimotor function. Additionally, this scientific proposal, along with the outstanding training environment in the Murthy lab and at the joint MD/PhD program at Princeton and Rutgers, will provide exceptional foundational training in preparation for my career as an independent physician scientist with my own laboratory.

项目概要 感知多感官信息并以适当的实时行为做出响应对于 过去的研究调查了一般大脑的正常交流和互动。 区域以及特定细胞响应不止一种类型的感官提示而放电，但尚未 精确定位了它们的突触前单峰伙伴（输入），这意味着所研究的细胞可能不是 此外，这些神经元本身并不驱动。 这在理解（1）多感觉神经元如何进行方面留下了空白。 直接从细胞和电路的单模输入获取其多模态特征检测属性 水平，（2）他们如何随着时间的推移整合多模态信号，以及（3）他们如何将这些信号转换为 动态运动反应，所有这些都发生在道德相关的和固有的相互作用中。 控制果蝇求爱的神经回路是一个成熟的模型 感觉处理和实时行为反应：在苍蝇求爱期间，雄性向雌性唱歌，并且 雌性感知歌曲并做出反应，这反过来又改变了雄性自身的求偶行为，这形成了一个复杂的过程。 在求偶循环中，我有模仿许多动物社交互动特性的“对话”。 发现了多细胞细胞和电路上的两个直接的单感觉汇聚点，它们已 它们本身被证明是驱动和调节稳健、可测量和固有的必要和充分的 雌性果蝇的行为，为解决上述差距提供了前所未有的机会。 通过新型全脑和半脑电子显微镜的分析确定了收敛点 突触分辨率的数据集。 该提案将直接阐明细胞、电路、 通过高分辨率行为跟踪分析，目标 1 将确定如何通过 整合视听信息的自然组合，两个多感觉神经元驱动道德 目标 2 将使用钙成像来确定果蝇雌性的相关行为。 求偶虚拟现实，这些神经元如何整合来自三个单感觉的听觉和视觉信号 总而言之，这项研究将显着扩展对脑细胞和电路如何处理的理解。 多感官信号并将其转化为动态运动反应，为 此外，这个科学建议， 以及 Murthy 实验室和 MD/PhD 联合项目出色的培训环境 普林斯顿大学和罗格斯大学将提供卓越的基础培训，为我的职业生涯做好准备 拥有自己实验室的独立医师科学家。