Uncovering the Neural Mechanisms that Flexibly Link Sensory Processing to Behavior

揭示将感觉处理与行为灵活联系起来的神经机制

• 批准号: 9924657
• 负责人: Mala Murthy
• 金额: $ 57.55万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9924657
• 关键词: Acoustics; Address; Animal Behavior; Animals; Arousal; Behavior; Behavioral; Behavioral Assay; Biological Models; Brain; Cells; Communication; Complex; Computer Models; Courtship; Cues; Data; Disease; Drosophila genus; Female; Foundations; Generations; Human; Hunger; Image; Impairment; Individual; Learning; Link; Mediating; Methods; Movement; Parkinson Disease; Partner Communications; Partner in relationship; Pattern; Perception; Population; Process; Research; Ritual compulsion; Sensory; Shapes; Side; Social Environment; Social Interaction; Stimulus; Structure; System; Thinking; Visual; auditory pathway; autism spectrum disorder; experience; flexibility; fly; male; millisecond; motor behavior; multimodality; neural circuit; neural correlate; neuromechanism; novel; relating to nervous system; response; sound; tool; transcriptomics; treadmill

Over the past eight years, my lab has pioneered studies of the acoustic communication system of Drosophila, to address fundamental questions related to the neural mechanisms underlying sensory perception and the generation of behaviors. Similar to other animals, flies produce and process patterned sounds during their mating ritual. Using a combination of novel behavioral assays, neural circuit perturbations, neural recordings, and computational modeling, we discovered that male song structure and intensity are continually sculpted by interactions with the female, over timescales ranging from tens of milliseconds to minutes. Building on this finding, we have gone on to dissect the neural mechanisms underlying the visual modulation of song patterning in males. Using a similar set of tools, we have also interrogated the female side of acoustic communication, and have successfully related song representations along the auditory pathway to changes in locomotor behavior, again across multiple timescales. My lab has developed several new methods to facilitate these studies, including methods for tracking and segmenting animal behavior, for population neural imaging, and for single-cell transcriptomics in the Drosophila brain. Our system and discoveries lay the essential foundation for now solving the bigger challenge of how an animal's internal state and experiences contribute to shaping these neural mechanisms. To do so, we will employ new computational models to identify the neural correlates of internal state. We will also use a new paradigm to induce learning during acoustic communication, and will characterize how learning shapes sensorimotor integration in this system. Finally, we will manipulate the hunger or arousal status of flies to determine, again at the cellular level, how long timescale modulation of neural activity shapes fast timescale sensorimotor processes. These new research directions will leverage the methods we have optimized for the recording and analysis of neural and behavioral data, in addition to incorporating new methods for recording activity in behaving flies that experience naturalistic, multimodal courtship stimuli timed to their movements on a spherical treadmill. What we discover in this system will reveal fundamental principles regarding how brains mediate perceptions, thoughts, actions, and ultimately the ability to communicate with another individual.

在过去的八年里，我的实验室率先研究了果蝇的声音通讯系统， 解决与感官知觉的神经机制相关的基本问题， 行为的生成。与其他动物类似，苍蝇在其活动期间产生并处理模式化的声音。 交配仪式使用新的行为分析，神经回路扰动，神经记录， 和计算模型，我们发现，男性歌曲的结构和强度不断雕刻， 与雌性的互动，时间跨度从几十毫秒到几分钟不等。在此基础上 发现，我们已经深入剖析了潜在的神经机制的视觉调制的歌曲模式 在男性中。使用一套类似的工具，我们也询问了女性的声音交流， 并成功地将沿着听觉通路的歌曲表征与运动的变化联系起来 行为，同样是在多个时间尺度上。我的实验室开发了几种新方法来促进这些 研究，包括跟踪和分割动物行为的方法，群体神经成像， 果蝇大脑中的单细胞转录组学我们的系统和发现为以下方面奠定了重要基础： 现在解决了一个更大的挑战，即动物的内部状态和经历如何有助于塑造这些 神经机制。为了做到这一点，我们将采用新的计算模型来确定神经相关的 内部状态。我们还将使用一种新的范式来诱导声学通信过程中的学习，并将 描述学习如何塑造这个系统中的感觉运动整合。最后，我们将操纵 饥饿或唤醒状态的果蝇，以确定，再次在细胞水平上， 神经活动塑造快速时间尺度的感觉运动过程。这些新的研究方向将利用 我们已经优化了记录和分析神经和行为数据的方法， 采用新的方法记录果蝇的活动， 求爱刺激与它们在球形跑步机上的运动同步。我们在这个系统中的发现将揭示 关于大脑如何调节感知、思想、行动以及最终能力的基本原理 与另一个人交流。