Context-dependent neural processing of leg proprioception in Drosophila

果蝇腿部本体感觉的上下文相关神经处理

• 批准号: 10039477
• 负责人: Sweta Agrawal
• 金额: $ 10.16万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10039477
• 关键词: Affect; Afferent Neurons; Anatomy; Animals; Area; Attenuated; Auditory; Axon; Behavioral; Biophysics; Body part; Brain; Brain region; Calcium; Complex; Computer Models; Computing Methodologies; Cues; Data; Drosophila genus; Drosophila melanogaster; Electrophysiology (science); Environmental Wind; Evolution; Face; Feedback; Focus Groups; Functional disorder; GABA Receptor; Genetic; Goals; Image; Interneurons; Joints; Leg; Limb structure; Locomotion; Measures; Mechanoreceptors; Mentors; Monitor; Motion; Motor; Motor Neurons; Movement; Muscle; Nerve; Nervous system structure; Neurons; Non-linear Models; Organ; Paralysed; Pathway interactions; Phase; Physiology; Positioning Attribute; Postdoctoral Fellow; Posture; Proprioception; Proprioceptor; Publishing; Research; Running; Secure; Sensory; Shapes; Signal Transduction; Site; Spinal Cord; Structure; Synapses; System; Testing; Universities; Vertebrates; Walking; Washington; body position; cell type; equilibration disorder; expectation; experimental study; flexibility; fly; insight; kinematics; knock-down; limb movement; millisecond; motor behavior; motor control; motor learning; multimodality; patch clamp; post-doctoral training; relating to nervous system; response; skills; tenure track; tibia; two-photon; way finding

Proprioception is critical for effective motor control: dysfunctions of the proprioceptive system can impair balance, motor coordination, and motor learning. However, despite its importance, little is known about the initial stages of proprioceptive processing in any animal, nor how this information is modulated by behavioral state. I propose studying proprioception in the fly, D. melanogaster, whose proprioceptive system is more experimentally accessible than that of vertebrates, but still analogous in its organization and function. I will combine experimental and computational methods to study the flow of information from the proprioceptive sensory structure, the femoral chordotonal organ, into genetically identifiable downstream circuits. In particular, I will characterize how neural encoding changes during self vs. externally-generated movements, and how proprioceptive information enters the brain to inform motor planning. Test how perturbing specific inputs changes central encoding of imposed tibia movements. I will use patch- clamp electrophysiology to record the activity of second-order proprioceptive neurons while moving the leg along naturalistic and broadband, pseudo-random trajectories. I will then build a linear/nonlinear model to determine the computations performed by each cell type. I will perturb inputs to central neurons and determine how these perturbations alter neural encoding of leg movements. Test the hypothesis that self- vs. externally-generated motions are differently encoded by some neurons. I will record the activity of second-order neurons while the fly moves its leg. I will then replay those movements and determine which neurons differently encode self- vs. externally-generated movements. I will characterize how a neuron’s encoding changes and determine if there is an internal estimate of state expectations. Determine how proprioceptive information entering the brain integrates with behavioral state and information from other mechanoreceptors. Preliminary anatomical data suggests that a region of the brain, the wedge, integrates multimodal mechanosensory cues from the legs and antennae. I will use 2-photon calcium imaging to determine what proprioceptive information is relayed to this area and whether leg movement attenuates antennal signals. I will then focus on how the central complex, a brain region important in motor planning, receives proprioceptive input. I will use intracellular recordings and calcium imaging to ask which central complex neurons encode proprioceptive information. My long-term goal is to run my own research group focused on the function and evolution of the fly proprioceptive system. Toward this end, my postdoctoral training is focused on the following goals: honing my computational skills, developing management and mentoring skills, publishing and presenting my research, and securing an independent, tenure-track position. I will be co-mentored by Drs. John Tuthill and Adrienne Fairhall in the Physiology and Biophysics department at the University of Washington.

本体感觉对于有效的运动控制至关重要：本体感觉系统功能障碍会损害 平衡、运动协调和运动学习。然而，尽管它很重要，但人们对最初的情况知之甚少。 任何动物本体感觉处理的阶段，以及这些信息如何通过行为状态调节。我 提议研究黑腹果蝇的本体感觉，其本体感觉系统更具实验性 比脊椎动物更容易接近，但其组织和功能仍然相似。我会结合实验 和计算方法来研究来自本体感觉结构的信息流， 股骨弦音器官，进入可遗传识别的下游回路。我将特别描述如何 自我运动与外部产生的运动期间神经编码的变化，以及本体感受信息如何变化 进入大脑以告知运动计划。 测试扰动特定输入如何改变施加的胫骨运动的中心编码。我将使用补丁- 钳电生理学记录腿部移动时二阶本体感觉神经元的活动 自然主义和宽带、伪随机轨迹。然后我将建立一个线性/非线性模型来确定 每种细胞类型执行的计算。我将扰乱中枢神经元的输入并确定这些神经元如何 扰动改变腿部运动的神经编码。 测试以下假设：一些神经元对自身产生的运动与外部产生的运动进行不同的编码。我 当苍蝇移动它的腿时，它将记录二级神经元的活动。然后我会重放这些动作 并确定哪些神经元对自身产生的运动与外部产生的运动进行不同的编码。我将表征 神经元的编码如何变化并确定是否存在状态期望的内部估计。 确定进入大脑的本体感受信息如何与行为状态和信息整合 来自其他机械感受器。初步的解剖数据表明，大脑的一个区域，即楔形区域， 集成了来自腿部和触角的多模式机械感觉线索。我将使用 2 光子钙成像 确定哪些本体感觉信息被传递到该区域以及腿部运动是否会减弱触角 信号。然后我将重点讨论中央复合体（在运动规划中重要的大脑区域）如何接收 本体感受输入。我将使用细胞内记录和钙成像来询问哪些中央复杂神经元 编码本体感受信息。 我的长期目标是建立自己的研究小组，专注于果蝇的功能和进化 本体感受系统。为此，我的博士后培训重点关注以下目标： 计算技能，发展管理和指导技能，出版和展示我的研究，以及 确保获得独立的终身教职职位。我将由博士共同指导。约翰·塔希尔和艾德丽安·费尔霍尔 在华盛顿大学生理学和生物物理学系。