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

基本信息

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
项目类别：
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

项目摘要

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，但人们对它的最初了解却知之甚少。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。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，我将结合实验。和计算方法来研究来自本体感觉结构的信息流，我将特别描述如何将股骨弦音器官转化为可遗传识别的下游回路。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 patch-。钳电生理学记录腿部移动时二阶本体感觉神经元的活动然后，我将构建一个线性/非线性模型来确定自然主义和宽带伪随机轨迹。我将干扰每种细胞类型执行的计算，并确定这些输入是如何产生的。扰动改变腿部运动的神经编码。测试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编码的假设。当苍蝇移动它的腿时，我会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我产生的运动与外部产生的运动进行不同的编码，我将对其进行表征。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的初步解剖数据表明，大脑的一个区域，楔形，集成来自腿部和触角的多模态机械感觉线索，我将使用 2 光子钙成像来进行。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然后我将重点讨论中央复合体（运动规划中重要的大脑区域）如何接收信号。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为此，我的博士后培训重点关注以下目标：磨练我的本体感觉系统。发展计算技能、管理和指导技能，出版和展示我的研究，以及我将得到 John Tuthill 和 Adrienne Fairhall 博士的共同指导。在华盛顿大学生理学和生物物理学系。