Reverse Engineering the Brain Stem Circuits that Govern Exploratory Behavior

对控制探索行为的脑干回路进行逆向工程

基本信息

批准号：
10199070
负责人：
Martin Deschenes
金额：
$ 298.96万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-15 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10199070
关键词：
3-Dimensional Affect Algorithms Anatomy Atlases Behavior Behavioral Birth Brain Brain Stem Breathing Cell Nucleus Cells Cephalic Collaborations Communities Complement Computer Models Data Data Science Core Data Set Decision Making Dedications Development Disease Education Electrophysiology (science)Engineering Esthesia Exploratory Behavior Feedback Food Generations Genetic Goals Head Histology Individual Interruption Joints Label Lead Life Link Literature Machine Learning Maps Measures Mechanics Methods Modeling Modernization Molecular Molecular Genetics Motion Motor Motor output Movement Muscle Nature Neuroanatomy Neurons Neurosciences Nose Output Pathway interactions Pattern Periodicity Phenotype Plants Population Procedures Publications Recording of previous events Regulation Research Project Grants Reticular Formation Rodent Role Schools Sensory Signal Transduction Specificity Structure Sum System Techniques Texture Tongue Training Vibrissae active control base control theory design digital experimental study in vivo innovation motor control neuron component neuronal circuitry optogenetics orofacial physical model platform-independent programs reconstruction sensor sensory input theories tool

项目摘要

Overview - Abstract Brainstem function is necessary for life-sustaining functions such as breathing and for survival functions, such as foraging for food. Individual motor actions are activated by specific brainstem cranial motor nuclei. The specificity of individual motor actions reflects the participation of motor nuclei in circuits within closed loops between sensors and muscle actuators. However, these loops are also nested and connect to feedback and feedforward pathways, which underlie coordination between orofacial motor actions. A key question for this proposal is how different actions are coordinated to form a rich repertoire of behaviors, such as rhythmic motions linked to breathing, and the orchestrated displacements of the head, nose, tongue, and vibrissae during exploration. We postulate that the best candidate interface for orofacial motor coordination are premotor and pre2motor neuron populations in the brainstem reticular formation: these neurons project to cranial motor nuclei, receive descending inputs from outside of the brainstem, and interconnected to each other. Our approach exploits and expands upon a broad spectrum of innovative experimental tools. These include state-of-the-art behavioral methods to study motor actions and their coordination into behaviors. From an experimental perspective, the underlying neuronal circuitry for each orofacial motor action may be accessed via transsynaptic transport starting at the muscle activators or associated sensors in the periphery. These studies will make use of molecular, genetic, and functional labeling methods to enable cell phenotyping and circuit tracing. These data will establish the "Components", i.e., brainstem nuclei connectivity for all Research Projects. These studies are complemented by in vivo electrophysiology and optogenetics in order measure and perturb the signal flow during exploration and decision-making: these studies will establish orofacial “Wiring Diagrams”. The sum of these techniques will permit us to elucidate the functions of intrinsic brainstem circuits and their modulation by descending pathways. Our data will be integrated in two ways. First we will begin development of computational models of the dynamics of active sensing by the orofacial motor plant and brainstem circuits. These will initially focus on the vibrissa system, starting with characterizations of mechanics and mechano-neuronal transformations of vibrissa movement and extending to exploration of brainstem circuits that drive vibrissa set-point and rhythmic whisking. Finally, vibrissa feedforward pathways will be computationally modeled to explore how sensory input affects vibrissa dynamics. Second, to record connectivity data that arises from our experimental tracing studies, we will construct an Trainable Texture-based Digital Atlas that utilizes machine learning to automate anatomical annotation of brainstem nuclei. The Atlas is designed to allow accurate 3D alignment of labeled neurons, even when labeled neurons reside in small sub-regions outside of well-defined brainstem nuclei, based on triangulation to Atlas landmark structures. Further, digitization of serially sectioned brain data sets allows 3D reconstruction and alignment of small brainstem subregions as well as the collation of this data from different brains into the same Atlas. Our proposed program on brainstem circuitry and dynamics will yield general lessons about the nature of neuronal computation. The analytic and anatomical tools developed for these studies will be made available through our data science core to the larger neuroscience community.

概述 - 摘要脑干功能对于维持生命的功能（例如呼吸）和生存功能是必需的，例如寻找食物是由特定的脑干颅运动核激活的。个体运动动作的特异性反映了闭环内运动核团的参与然而，这些循环也是嵌套的并连接到反馈和前馈路径是口面部运动动作之间协调的一个关键问题。提案是如何协调不同的行动以形成丰富的行为库，例如有节奏的与呼吸相关的运动，以及头、鼻子、舌头和触须的精心安排的位移在探索过程中，我们假设口面部运动协调的最佳候选接口是运动前接口。脑干网状结构中的前运动神经元群：这些神经元投射到颅运动细胞核，接收来自脑干外部的下行输入，并相互连接。我们的方法利用并扩展了广泛的创新实验工具，其中包括。最先进的行为方法来研究运动动作及其协调行为。从实验的角度来看，每个口面部运动动作的底层神经回路都可以被访问通过从周围肌肉激活器或相关传感器开始的突触运输。研究将利用分子、遗传和功能标记方法来实现细胞表型分析和这些数据将建立“组件”，即所有研究的脑干核连接。这些研究得到了体内电生理学和光遗传学的补充，以便测量和研究。扰乱探索和决策过程中的信号流：这些研究将建立口面部“布线” 这些技术的总和将使我们能够阐明内在脑干回路的功能。及其通过下行通路的调节。我们的数据将以两种方式整合。首先，我们将开始开发计算模型。口面部运动植物和脑干回路主动传感的动力学这些最初将集中于触须系统，从力学特征和机械神经元转换开始触须运动并延伸至驱动触须设定点和节律的脑干回路的探索最后，将对触须前馈路径进行计算建模，以探索感官输入的方式。其次，记录我们的实验追踪研究产生的连接数据，我们将构建一个可训练的基于纹理的数字图集，利用机器学习来自动化脑干核的解剖注释 Atlas 旨在实现标记的精确 3D 对齐。神经元，即使标记的神经元位于明确脑干核之外的小子区域中，基于对阿特拉斯地标结构的三角测量此外，连续切片的大脑数据集的数字化。允许小脑干分区的 3D 重建和对齐以及来自不同的大脑进入同一个阿特拉斯。我们提出的关于脑干电路和动力学的计划将产生有关脑干本质的一般教训为这些研究开发的分析和解剖工具将可供使用。通过我们的数据科学核心扩展到更大的神经科学界。