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（由申请人提供）：为了解决奥巴马大脑计划背后的核心问题，以更好地理解复杂大脑回路的功能，我们提出了一个多尺度记录和数据分析项目，以研究感觉皮层、运动皮层、多尺度方法将涉及对被训练执行奖励性运动任务的头部固定行为小鼠进行细胞、网络和系统水平的同步记录。胡须表示“GO”或“STOP”提示，并且将在细胞水平上分析由此产生的启动或抑制运动的大脑过程，采用自动修补技术的体内全细胞记录将产生有关感觉和运动中单个神经元膜电位轨迹的详细信息。在网络层面上，多个单单元和局部场电位（LFP）记录将允许评估跨多个皮层层的局部群体动态以及在系统层面上的丘脑-皮质相互作用。表面使用新型转基因电压传感蛋白将允许以高达 200 Hz 的频率分辨率研究宏观活动模式的时空动力学，例如，同时记录数据将允许对细胞和网络动力学之间的关系进行多尺度分析。 ，将分析场电位波动与单个神经元膜动力学之间的关系，并有望对群体编码产生重要的见解。同样，通过成像获得的活动图与皮层 LFP 记录揭示的振荡网络活动之间的关系。是预计会对运动规划的组织产生重要的见解，我们的工作将特别关注β带（12-35 Hz）振荡在控制观察到的行为中的作用，因为β振荡在皮质中都具有令人信服的作用。此外，帕金森病患者的基底神经节和 6OHDA 训练的帕金森病啮齿动物模型中，β 振荡病理性过度表达，可能源于运动。因此，我们的指导假设是β振荡为大脑皮层提供了一个重要的支架。 为了测试运动计划和执行过程中大脑区域之间的通信，我们将通过对基底神经节传出、感觉皮层或运动皮层的个体发育刺激来人为地诱导β带活动，并分析由此产生的变化。总体而言，这些研究将行为啮齿类动物运动处理的系统神经生理学水平提高到一个新水平，并有望为跨多个大脑活动的组织提供基本见解。这些见解对于研究影响基底神经节的神经系统疾病（例如帕金森病、亨廷顿病和强迫症）的病理性大脑动力学非常有价值。