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.

项目摘要 感知多感官信息并以适当的实时行为做出响应对于 正常的沟通和与环境的互动。过去的研究调查了一般大脑 区域以及针对多种类型的感觉提示发射的特定细胞，但尚未 精确指出了突触前的单峰伴侣（输入），这意味着Studiod细胞可能不是 多感官收敛的直接点。此外，这些神经元本身并没有开车 反应灵敏和先天的运动行为。这留下了理解的差距（1）多感觉神经元如何 直接从细胞和电路的单峰输入中获取其多模式特征检测属性 级别，（2）它们如何随着时间的推移整合多模式信号，以及（3）它们如何将这些信号转换为 在伦理上相关和先天的互动期间，动态运动反应。 管理果蝇的神经电路，是Melanogaster求爱的求婚 感官处理和实时行为反应：在苍蝇求爱期间，男性向女性唱歌，以及 女性感知并回应歌曲，这反过来改变了男性的求爱行为。这形成一个复杂的 模仿许多动物社交互动的特性的“对话”。在求爱巡回赛中，我有 发现了两个直接的通用收敛点到具有多细胞细胞和电路，它们具有 他们被证明是必要的，足以驾驶和调节健壮，可衡量和先天 果蝇女性的行为，为解决上述差距提供了前所未有的机会。 通过分析新型的全脑和半脑电子显微镜来鉴定收敛点 突触分辨率的数据集。 该建议将直接阐明在细胞，电路， 和行为水平。通过高分辨率的行为跟踪测定，AIM 1将确定如何通过 整合视听信息的自然组合，两个多感官神经元在伦理上驱动一个 果蝇女性的相关行为。 AIM 2将确定在A中使用钙成像 求爱虚拟现实，那些神经元如何整合了三个独立性的听觉和视觉信号 输入。综上所述，这项研究将显着扩大对脑细胞和电路如何处理的理解 多感觉信号并将其转换为动态的电动机响应，为 对正常和无序的感觉运动功能的长期理解。此外，这项科学建议， 以及Murthy实验室的出色培训环境以及在联合MD/PHD计划中 普林斯顿和罗格斯将提供出色的基础培训，为我的职业做准备 我自己的实验室的独立物理科学家。