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: 10630079
• 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/10630079
• 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; 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 Interaction; Stimulus; Structure; System; Thinking; Visual; auditory pathway; autism spectrum disorder; experience; flexibility; fly; male; millisecond; motor behavior; multimodality; neural; neural circuit; neural correlate; neuroimaging; neuromechanism; novel; 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学通信系统，