Mechanosensory feature extraction for directed motor control

用于定向运动控制的机械感觉特征提取

• 批准号: 10202742
• 负责人: Rachel Wilson
• 金额: $ 35.62万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10202742
• 关键词: Address; Animals; Auditory; Axon; Behavior; Behavioral; Biological Models; Brain; Brain region; Calcium; Cell physiology; Cells; Characteristics; Code; Complement; Computational algorithm; Coupling; Cues; Data; Dependence; Disease; Distal; Drosophila genus; Electrophysiology (science); Environmental Wind; Failure; Force of Gravity; Frequencies; Genes; Goals; Head; Health; Human; Image; Individual; Lateral; Left; Leg; Link; Lobe; Measures; Mechanics; Membrane; Mental disorders; Methods; Motor; Motor Neurons; Movement; Nerve; Neurons; Odors; Optics; Organ; Organism; Pattern; Phenotype; Physiology; Population; Postural adjustments; Process; Property; Sensory; Side; Signal Transduction; Stimulus; Synapses; System; Testing; Therapeutic; Touch sensation; Walking; Whole-Cell Recordings; Work; behavior measurement; experimental study; extracellular; feature extraction; flexibility; fly; high dimensionality; imaging study; improved; in vivo; in vivo calcium imaging; innovation; insight; mechanical force; motor control; nervous system disorder; neural circuit; neuronal cell body; postsynaptic; postsynaptic neurons; relating to nervous system; response; sensor; sensory stimulus; somatosensory; sound; spatiotemporal; temporal measurement; vibration; voltage; Address; Animals; Auditory; Axon; Behavior; Behavioral; Biological Models; Brain; Brain region; Calcium; Cell physiology; Cells; Characteristics; Code; Complement; Computational algorithm; Coupling; Cues; Data; Dependence; Disease; Distal; Drosophila genus; Electrophysiology (science); Environmental Wind; Failure; Force of Gravity; Frequencies; Genes; Goals; Head; Health; Human; Image; Individual; Lateral; Left; Leg; Link; Lobe; Measures; Mechanics; Membrane; Mental disorders; Methods; Motor; Motor Neurons; Movement; Nerve; Neurons; Odors; Optics; Organ; Organism; Pattern; Phenotype; Physiology; Population; Postural adjustments; Process; Property; Sensory; Side; Signal Transduction; Stimulus; Synapses; System; Testing; Therapeutic; Touch sensation; Walking; Whole-Cell Recordings; Work; behavior measurement; experimental study; extracellular; feature extraction; flexibility; fly; high dimensionality; imaging study; improved; in vivo; in vivo calcium imaging; innovation; insight; mechanical force; motor control; nervous system disorder; neural circuit; neuronal cell body; postsynaptic; postsynaptic neurons; relating to nervous system; response; sensor; sensory stimulus; somatosensory; sound; spatiotemporal; temporal measurement; vibration; voltage

Summary This proposal addresses two fundamental questions: (1) How do neurons extract features of mechanosensory stimuli that are relevant for motor control? (2) How do central circuits create a flexible linkage between mechanosensory stimuli and behavior? These questions are relevant to human health because sensory processing and sensory-motor integration are disrupted in many neurological and psychiatric disorders. However, sensory processing and sensory-motor integration are not fully understood at the level of cellular mechanisms – i.e., at the level of neural connectivity, cellular physiology, and synaptic physiology. This level of mechanistic explanation is important to understanding why disease-linked genes produce their characteristic phenotypes. It is also important to developing better therapeutics. As a model system for gaining mechanistic insight into these brain functions, this project will focus on the largest mechanosensory organ in Drosophila (Johnston's organ) and the circuits and behaviors downstream from this organ. Johnston's organ neurons (JONs) encode deflections of the distal antennal segment. These deflections can result from an object touching the antenna, wind, postural changes, or sound. In essence, therefore, Johnston's organ has a range of functions – somatosensory, vestibular, and auditory. Different JON stimuli elicit different behaviors. These behaviors are variable and context-dependent (not stereotyped action patterns) and so we can use this system to study flexibility in sensory-motor coupling. Our first aim is to determine how JONs encode mechanical stimuli. To test the hypothesis that JONs are highly specialized for specific spatiotemporal features of antennal deflections, we will use a combination of in vivo calcium imaging, electrophysiology, and voltage imaging. Second, we will use in vivo whole cell recordings to test the hypothesis that central neurons postsynaptic to JONs can extract specific frequencies of antennal vibrations by virtue of their intrinsic electrical bandpass filtering characteristics. Third, we will perform in vivo whole cell recordings to investigate how mechanosensory signals are encoded at the level of third-order neurons, and how these signals are relayed to motor control centers. We hypothesize that wind and sound stimuli will be encoded by largely distinct neural channels. Fourth, we will combine whole-cell recording with simultaneous behavioral measurements to determine how mechanosensory cues from JONs steer walking direction in a context-dependent manner. We hypothesize that heading direction cues and context cues will converge at the level of descending motor control neurons that project to the ventral nerve cord. As a whole, this work will provide new insights into the neural computations that occur in mechanosensory processing and mechanosensory- motor integration, as well as the cellular mechanisms that implement these computations.

概括 该建议解决了两个基本问题： （1）神经元如何提取与运动控制相关的机理感觉刺激的特征？ （2）中央电路如何在机械学刺激和行为之间建立灵活的联系？ 这些问题与人类健康有关，因为感官处理和感觉运动整合被破坏 许多神经和精神病。但是，感觉处理和感觉运动的整合并不完全 了解细胞机制的水平 - 即在神经连通性，细胞生理和突触的水平上 生理。这种机械解释水平对于了解为什么疾病相关基因产生其 特征表型。这对于开发更好的治疗也很重要。作为获得的模型系统 对这些大脑功能的机械洞察力，该项目将重点放在果蝇中最大的机械感官上 （约翰斯顿的器官）以及该器官下游的电路和行为。约翰斯顿的器官神经元（JONS）编码 远端天线段的偏转。这些偏转可能是由接触天线，风， 姿势变化或声音。因此，本质上，约翰斯顿的器官具有一系列功能 - 体感，前庭， 和听觉。不同的乔恩刺激会引起不同的行为。这些行为是可变和上下文依赖性的（不是 刻板印象的动作模式），因此我们可以使用该系统来研究感觉运动耦合的灵活性。我们的第一个目标是 确定Jons如何编码机械刺激。测试Jons高度专业的假设 触角挠度的时空特征，我们将使用体内钙成像，电生理学的组合， 和电压成像。其次，我们将使用体内全细胞记录来检验中枢神经元的假设 突触后对Jons可以通过固有的电带通道提取触角振动的特定频率 过滤特征。第三，我们将执行体内整个细胞记录，以研究机械学信号 在三阶神经元的水平上编码，以及如何将这些信号传递到运动控制中心。我们 假设风和声音刺激将由大部分不同的神经通道编码。第四，我们将结合 使用简单的行为测量来确定JONS的机制线索如何进行全细胞记录 以上下文依赖的方式转向行走方向。我们假设指导方向提示和上下文提示将 在向腹神经绳投射的下降运动控制神经元的水平上收敛。总体而言，这项工作 将提供有关机理增强处理和机理感知的神经计算的新见解。 电机整合以及实施这些计算的细胞机制。