Mechanosensory feature extraction for directed motor control

用于定向运动控制的机械感觉特征提取

基本信息

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
项目类别：
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

项目摘要

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.

概括该提案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械感觉刺激特征？（2）中枢回路如何在机械感觉刺激和行为之间建立灵活的联系？这些问题与人类健康相关，因为感觉处理和感觉运动整合在许多神经和精神疾病然而，感觉处理和感觉运动整合并不完全。在细胞机制层面上理解——即在神经连接、细胞生理学和突触层面这种水平的机制解释对于理解疾病相关基因产生的原因很重要。特征表型对于开发更好的治疗方法也很重要。为了深入了解这些大脑功能，该项目将重点关注果蝇最大的机械感觉器官（约翰斯顿器官）以及该器官下游的电路和行为神经元 (JON) 进行编码。远端触角部分的偏转这些偏转可能是由于物体接触天线、风、因此，从本质上讲，约翰斯顿的器官具有一系列功能——体感、前庭、不同的 JON 刺激会引发不同的行为。刻板的动作模式），因此我们可以使用这个系统来研究感觉-运动耦合的灵活性。确定 JON 如何编码机械刺激来检验 JON 高度专业化的假设。触角偏转的时空特征，我们将结合体内钙成像、电生理学、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。 JON 的突触后可以凭借其固有的电带通提取天线振动的特定频率第三，我们将进行体内全细胞记录以研究机械感觉信号如何。在三级神经元水平上编码，以及这些信号如何传递到运动控制中心。四、我们将结合全细胞记录与同时行为测量以确定 JON 的机械感觉线索以依赖于上下文的方式引导行走方向，我们勇敢地面对方向提示和上下文提示。汇聚在投射到腹神经索的下行运动控制神经元的水平上。将为机械感觉处理和机械感觉中发生的神经计算提供新的见解运动整合，以及实现这些计算的细胞机制。