MULTISCALE ANALYSIS OF SENSORY-MOTOR CORTICAL GATING IN BEHAVING MICE

 描述(申请人提供)：为了更好地了解复杂大脑回路的功能，解决奥巴马大脑倡议的核心问题，我们提出了一个多尺度记录和数据分析项目，以研究运动规划和执行过程中感觉皮质、运动皮质和基底节之间的动态相互作用。多尺度方法将包括在细胞、网络和系统水平上对头部固定行为的小鼠进行同步记录，这些小鼠接受了执行有奖励的运动任务的训练。传递到胡须的感觉刺激将表示开始或停止的提示，并将分析由此产生的启动或抑制运动的大脑过程。在细胞水平上，使用自动配对技术的活体全细胞记录将在这项任务中提供关于感觉和运动皮质中单个神经元的膜电位轨迹的详细信息。在网络一级，多个单一单位和局域场电位(LFP)记录将允许评估多层大脑皮层和丘脑-大脑皮层相互作用的局部种群动态。在系统水平上，使用新型转基因电压传感蛋白对大脑皮层表面进行电压成像将允许以高达200赫兹的频率分辨率研究宏观活动模式的时空动力学。同时记录数据将允许对蜂窝和网络动态之间的关系进行多尺度分析。例如，将分析场电位波动和单个神经元的膜动力学之间的关系，并有望对种群编码产生重要的见解。同样，通过成像获得的活动图与大脑皮质LFP记录揭示的振荡网络活动之间的关系有望导致对运动规划的组织的重要见解。我们的工作将特别关注β波段(12-35赫兹)振荡在控制观察到的行为中的作用，因为β振荡已被令人信服地牵涉到皮质感觉过程以及运动控制中。此外，在帕金森氏症患者和6OHDA减轻帕金森综合征啮齿动物模型中，β振荡在病理上过度表达，可能的来源是运动皮质。因此，我们的指导性假设是，β振荡为 运动计划和执行过程中大脑区域之间的交流。为了测试β振荡和运动加工之间的因果关系，我们将通过个体发育刺激基底神经节传出、感觉皮质或运动皮质来人工诱导β带活动，并分析刺激和非刺激区域行为和脑动力学的结果变化。总体而言，这些研究将把行为啮齿动物运动处理的系统神经生理学水平提高到一个新的水平，并有望提供对多个尺度上大脑活动组织的基本见解。这些见解将在帕金森氏病、亨廷顿病和强迫症等影响基底节的神经疾病的病理脑动力学研究中发挥重要作用。

 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.