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: 10828249
• 负责人: Edna Normand
• 金额: $ 5.27万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 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 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10828249
• 关键词: Address; Afferent Neurons; 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; behavioral response; brain cell; career; connectome data; 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 integration; sensory processing disorder; sensory stimulus; 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反应， 与环境的正常沟通和互动。过去的研究调查了一般的大脑 区域以及特定的细胞，响应一种以上的感觉线索，但没有 他们指出了他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突触前的单峰伙伴。 多感觉会聚的直接点。此外，这些神经元本身并没有驱动 反应和先天运动行为。这在理解（1）多感觉神经元如何 直接从单元和电路处的单峰输入获得它们的多模态特征检测特性 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，所有这些都发生在行为学相关和先天的相互作用中。 控制果蝇求偶的神经回路是一个很好的模型， 感觉处理和实时行为反应：在苍蝇求偶期间，雄性对雌性唱歌， 雌性感知并回应歌声，这反过来又改变了雄性自己的求偶行为。这就形成了一个复杂的 “对话”，模仿许多动物的社会互动的属性。在求偶圈里，我有 发现了两个直接的unisensory收敛点到多细胞细胞和电路， 它们本身已被证明是必要的，足以驱动和调节强大的，可测量的，和先天的 果蝇雌性的行为，提供了一个前所未有的机会，以解决上述差距。 通过分析新的全脑和半脑电子显微镜来确定会聚点 突触分辨率的数据集。 这个建议将直接阐明多感觉整合在细胞，电路， 和行为水平。通过高分辨率的行为跟踪分析，目标1将确定如何， 整合视听信息的自然组合，两个多感觉神经元在行为学上驱动一个 果蝇雌性的相关行为。目标2将确定，使用钙成像在行为苍蝇在一个 求爱虚拟现实，这些神经元如何整合听觉和视觉信号，从他们的三个unisensory 输入。总的来说，这项研究将大大扩展对脑细胞和回路如何处理的理解。 多感官信号，并将其转化为动态运动反应，为 长期了解正常和紊乱的感觉运动功能。此外，这一科学建议， 沿着在Murthy实验室和联合MD/PhD项目的优秀培训环境， 普林斯顿大学和罗格斯大学，将提供特殊的基础训练，为我的职业生涯做准备， 拥有自己实验室的独立医生科学家