Context-dependent neural processing of leg proprioception in Drosophila

本体感觉对有效的运动控制至关重要：本体感觉系统的功能障碍可能会损害 平衡、运动协调和运动学习。然而，尽管它很重要，人们对最初的 任何动物的本体感觉过程的阶段，也不知道这一信息是如何被行为状态调节的。我 建议研究苍蝇的本体感觉，它的本体感觉系统更多地是实验性的。 比脊椎动物更容易接近，但在组织和功能上仍然相似。我将结合实验 以及研究本体感觉结构的信息流的计算方法， 股骨节律器官，进入基因可识别的下游回路。特别是，我将描述如何 神经编码在自身产生的运动与外部产生的运动中的变化，以及本体感觉信息如何 进入大脑，告知运动计划。 测试干扰特定输入如何改变强加的胫骨运动的中央编码。我会用补丁- 钳夹电生理学记录腿部运动时二级本体感受性神经元的活动 自然的、宽带的、伪随机的轨迹。然后，我将构建一个线性/非线性模型来确定 每种单元格类型执行的计算。我将扰乱中枢神经元的输入，并确定这些 扰动改变了腿部运动的神经编码。 测试这一假设，即某些神经元对自身和外部产生的运动进行不同的编码。我 将记录苍蝇移动腿时二阶神经元的活动。然后我会重播这些动作 并确定哪些神经元对自身和外部产生的运动进行不同的编码。我将描述一下 神经元的编码是如何变化的，并决定是否存在状态预期的内部估计。 确定进入大脑的本体感觉信息如何与行为状态和信息相结合 来自其他机械感受器。初步的解剖学数据表明，大脑的一个区域，楔形脑区， 集成了来自腿部和触角的多模式机械传感信号。我将使用双光子钙成像技术来 确定哪些本体感觉信息传递到该区域，以及腿部运动是否会削弱触角 信号。然后我将集中讨论中央复合体，一个在运动规划中很重要的大脑区域，如何接受 本体感觉输入。我将使用细胞内记录和钙成像来询问哪些中枢复合体神经元 对本体感觉信息进行编码。 我的长期目标是运营自己的研究小组，专注于苍蝇的功能和进化 本体感觉系统。为此，我的博士后培训集中在以下目标：磨练我的 计算技能，发展管理和指导技能，发表和展示我的研究成果，以及 获得一个独立的终身教职职位。我将由John Tuthill博士和Adrienne FairHall博士共同指导 在华盛顿大学生理学和生物物理系。

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.