MULTISCALE ANALYSIS OF SENSORY-MOTOR CORTICAL GATING IN BEHAVING MICE

行为小鼠感觉运动皮质门控的多尺度分析

• 批准号: 9012601
• 负责人: DIETER JAEGER
• 金额: $ 61.43万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9012601
• 关键词: Address; Affect; Animal Model; Area; Attention; Basal Ganglia; Basic Science; Behavior; Behavioral; Brain; Cells; Clinical; Code; Communication; Complex; Coupled; Cues; Data; Data Analyses; Decision Making; Deep Brain Stimulation; Disease; Dystonia; Electrodes; Frequencies; Functional disorder; Head; Huntington Disease; Image; Individual; Instruction; Link; Locomotion; Maps; Membrane Potentials; Methods; Motor; Motor Cortex; Motor output; Movement; Mus; Nervous System Physiology; Neurons; Output; Parkinson Disease; Parkinsonian Disorders; Patients; Pattern; Performance; Population; Population Dynamics; Process; Proteins; Public Health; Research; Resolution; Rewards; Rodent; Role; Sensory; Sensory Ganglia; Sensory Process; Site; Source; Stimulus; Stream; Substantia nigra structure; Surface; Synapses; System; Technology; Testing; Thalamic structure; Time; Training; Transgenic Organisms; Ursidae Family; Vibrissae; Whole-Cell Recordings; Work; awake; base; extracellular; in vivo; information processing; innovation; insight; locomotor tasks; motor control; nervous system disorder; neurophysiology; novel; optogenetics; overexpression; public health relevance; relating to nervous system; scaffold; sensor; sensory cortex; sensory input; sensory stimulus; temporal measurement; tool; voltage

 DESCRIPTION (provided by applicant): To address the core question underlying the Obama Brain Initiative to better understand the function of complex brain circuits, we propose a multi-scale recording and data analysis project to study the dynamical interactions between sensory cortex, motor cortex, and the basal ganglia in the process of motor planning and execution. The multi-scale approach will involve simultaneous recordings at the cellular, network, and systems level in head-fixed behaving mice trained to perform a rewarded locomotor task. Sensory stimuli delivered to the whiskers will denote GO or STOP cues, and resulting brain processes initiating or suppressing movement will be analyzed. At the cellular level, in vivo whole cell recordings employing autopatcher technology will yield detailed information on the membrane potential trajectory of individual neurons in the sensory and motor cortex in this task. At the network level multiple single unit and local field potential (LFP) recordings will allow the assessment of local population dynamics across multiple layers of cortex and for thalamo-cortical interactions. At the systems level, voltage imaging of the cortical surface using novel transgenic voltage sensing proteins will allow the study of spatio-temporal dynamics of macroscopic activity patterns with a frequency resolution of up to 200 Hz. Recording data simultaneously will allow for a multi-scale analysis of the relations between cellular and network dynamics. For example, the relationship between fluctuations in the field potential and the membrane dynamics of single neurons will be analyzed and is expected to yield important insights into population coding. Similarly, the relation between activity maps obtained with imaging and oscillatory network activity revealed by LFP recordings of cortex is expected to result in important insights into the organization of motor planning. Our work will pay specific attention to the role of beta band (12-35 Hz) oscillations in the control of the observed behavior, because beta oscillations have been implicated convincingly both in cortical sensory processes as well as motor control. Further, beta oscillations are pathologically overexpressed in the basal ganglia of Parkinson's patients and 6OHDA lessoned rodent animal models of Parkinsonism with a likely source in motor cortex. Thus, our guiding hypothesis is that beta oscillations provide an important scaffold to the communication between brain areas in the process of motor planning and execution. To test the causal relation between beta oscillations and motor processing we will artificially induce beta band activity with ontogenetic stimulation of basal ganglia efferent, sensory cortex, or motor cortex and analyze resulting changes in behavior and brain dynamics in stimulated and non-stimulated areas. Overall, these studies will raise the level of systems neurophysiology of motor processing in the behaving rodent to a new level, and are expected to provide fundamental insights into the organization of brain activity across multiple scales. These insights will be invaluable in studies of pathological brain dynamics in neurological disorders affecting the basal ganglia such as Parkinson's disease, Huntington's disease and OCD.

 描述（由适用提供）：解决奥巴马大脑计划的核心问题，以更好地了解复杂的大脑电路的功能，我们提出了一个多尺度记录和数据分析项目，以研究Sensory Cortex，Motor Cortex和基本神经节在运动计划和执行过程中的动态相互作用。多尺度方法将在训练有素的运动型小鼠中，涉及蜂窝，网络和系统级别的简单录制，以执行奖励的运动任务。传递到晶须的感觉刺激将表示或停止提示，并且将分析引发或抑制运动的大脑过程。在细胞水平上，使用自动捕获器技术的体内全细胞记录将在此任务中获得有关感觉和运动皮层中各个神经元的膜电位轨迹的详细信息。在网络级别，多个单元和局部现场电位（LFP）记录将允许评估多层皮质和丘脑 - 皮质相互作用的局部人群动态。在系统级别，使用新型的转基因电压传感蛋白对皮质表面的电压成像将允许研究宏观活性模式的空间 - 周期动力学，其频率分辨率高达200 Hz。记录数据仅允许对蜂窝和网络动态之间关系的多尺度分析。例如，将分析现场电位波动与单个神经元的膜动力学之间的关系，并有望对人群编码产生重要的见解。同样，通过成像和振荡性网络活动获得的活动图之间的关系预计会导致对运动计划组织的重要见解。我们的工作将特别注意β频段（12-35 Hz）振荡在控制观察到的行为中的作用，因为在皮质感觉过程和运动控制中都令人信服地实施了β振荡。此外，在帕金森患者的低音神经节中，β振荡在病理上过表达，而6ohda Lessond rodent动物模型的帕金森主义模型则可能是运动皮层的来源。这就是我们的指导假设是，β振荡为 在运动计划和执行过程中，大脑区域之间的通信。为了测试β振荡与运动加工之间的灾难性关系，我们将通过对基本神经节有效，感觉皮层或运动皮层的基本发育刺激进行人工诱导β带活性，并分析刺激和非刺激区域的行为和脑动力学的变化。总体而言，这些研究将提高行为啮齿动物的运动处理系统的系统神经生理学水平，并有望为跨多个尺度的大脑活动组织提供基本的见解。这些见解将在影响基础神经节（例如帕金森氏病，亨廷顿氏病和强迫症）的神经系统疾病中的病理脑动力学研究中无价。