MULTISCALE ANALYSIS OF SENSORY-MOTOR CORTICAL GATING IN BEHAVING MICE

 描述（由申请人提供）：为了解决奥巴马脑倡议的核心问题，以更好地理解复杂脑回路的功能，我们提出了一个多尺度记录和数据分析项目，以研究运动规划和执行过程中感觉皮层、运动皮层和基底神经节之间的动态相互作用。多尺度方法将涉及在细胞、网络和系统水平上同时记录头部固定行为的小鼠，这些小鼠被训练来执行奖励运动任务。传递到胡须的感官刺激将表示GO或STOP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，采用自动匹配器技术的体内全细胞记录将产生关于该任务中感觉和运动皮层中单个神经元的膜电位轨迹的详细信息。在网络水平上，多个单个单元和局部场电位（LFP）记录将允许跨多层皮层和丘脑-皮层相互作用评估局部群体动态。在系统水平上，使用新的转基因电压传感蛋白的皮层表面的电压成像将允许宏观活动模式的时空动态的研究，频率分辨率高达200 Hz。同时记录数据将允许对细胞和网络动态之间的关系进行多尺度分析。例如，场电位波动和单个神经元的膜动力学之间的关系将被分析，并有望产生重要的见解群体编码。类似地，通过成像获得的活动图与皮层的LFP记录揭示的振荡网络活动之间的关系预计将导致对运动规划组织的重要见解。我们的工作将特别关注β波段（12-35 Hz）振荡在控制所观察到的行为中的作用，因为β振荡在皮层感觉过程和运动控制中都有令人信服的牵连。此外，β振荡在帕金森病患者的基底神经节和帕金森症的6 OHDA教训啮齿动物模型中病理性过表达，可能来源于运动皮层。因此，我们的指导假设是，β振荡提供了一个重要的支架， 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振荡和运动处理之间的因果关系，我们将通过基底神经节传出神经、感觉皮层或运动皮层的个体发育刺激人工诱导β带活动，并分析刺激和非刺激区域中的行为和大脑动力学变化。总的来说，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，并有望为跨多个尺度的大脑活动组织提供基本见解。这些见解将是非常宝贵的研究病理脑动力学的神经系统疾病，影响基底神经节，如帕金森氏病，亨廷顿氏病和强迫症。

 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.