Linking membrane voltage dynamics to fMRI measurement of functional connectivity in resting state and task related activities

项目摘要 功能连接性(Fc)已被发现在一系列其他难以区分的疾病中发生改变 各州。最常用的非侵入性研究全脑FC网络组织的工具是Functional 磁共振成像(FMRI)。功能磁共振成像依靠间接和不分青红皂白的活动测量，通过 血氧水平依赖(BOLD)对比机制。通过捕捉大胆信号中的波动 功能磁共振成像可以检测到大脑区域之间的远程同步，无论是在休息时还是在执行 具体任务。这些区域被推断为在功能上相连，并被认为涉及同步性 通过可塑性连接在一起的具有共同功能的神经元群体。释义 来自BOLD功能磁共振成像研究的FC网络目前受限于1)功能磁共振BOLD信号的依赖性 血流动力学变化作为神经活动的代用品和2)对机制基础的有限理解 在行为相关的纵向重组的背景下，对于FC。我的长期目标是做得更好 了解行为相关多区域环路中BOLD和神经活动之间的关系 高级大脑网络分析。一旦我们知道了血管和神经的变化是如何影响FC的，基础 对于网络功能障碍，可以利用功能磁共振成像提供更强大的基于功能磁共振成像的疾病检测。 在这个拟议的项目中，我将使用EMX1-CRE小鼠表达一种新的JEDI-1P电压荧光蛋白 穿过背侧皮质的兴奋性神经元。这种电压传感器有很大的光谱频带，允许我们记录 慢速、亚阈值电压活动和快速伽马频段活动。广域光学成像将是 结合功能磁共振成像，将FC中神经元的变化与fMRI测量的血流动力学变化联系起来。在目标1中，我 将这些绝地-1P成像在静息状态下建立膜电压动态之间的对应关系 以及用于静息状态功能连接网络的功能磁共振成像。在目标2中，我将训练这些小鼠执行 感觉运动任务。我会在任务训练中想象他们，以评估由于学习而导致的FC变化。我假设 FMRI BOLD和神经活动之间的相关性将是地区性的，对于静息状态和 在任务培训方面，后者将显著加强与任务有关的领域之间的职能分工。完成 这些目标将决定用BOLD观察到的功能网络如何与神经活动相关，并将提供 对FC如何反映感觉运动任务学习中与行为相关的变化的见解。这将导致 更敏锐地理解神经网络活动的特性、其相关性以及如何利用它 未来的功能磁共振研究。

PROJECT ABSTRACT Functional connectivity (FC) has been found to be altered in a wide range of otherwise indistinguishable disease states. The most common tool to non-invasively study the organization of brain-wide FC networks is functional magnetic resonance imaging (fMRI). fMRI relies on an indirect and indiscriminate measure of activity through the blood oxygen level-dependent (BOLD) contrast mechanism. By capturing fluctuations in the BOLD signal fMRI can detect distant synchronization between brain regions either at rest or during the performance of a specific task. These regions are inferred to be functionally connected and are thought to involve the synchrony of neuronal populations involved in a common function that are wired together through plasticity. Interpretation of FC networks derived from BOLD fMRI studies is currently limited by 1) the dependence of fMRI BOLD signals on hemodynamic changes as a proxy for neural activity and 2) a limited understanding of the mechanistic basis for FC in the context of behaviorally relevant longitudinal reorganizations. My long-term goal is to better understand the relationship between BOLD and neural activity in behaviorally relevant multi-regional circuits to advance brain network analysis. Once we know how both vascular and neural changes influence FC, the basis for network dysfunctions can be exploited with fMRI providing more robust fMRI-based disease detection. In this proposed project, I will use EMX1-Cre mice expressing a novel JEDI-1P voltage fluorescent protein in excitatory neurons across dorsal cortex. This voltage sensor has a large spectral band, allowing us to record both slow, subthreshold voltage activity, and fast gamma band activity. Wide-field optical imaging will be combined with fMRI to link neuronal changes in FC to hemodynamic changes measured with fMRI. In Aim 1 I will image these JEDI-1P at resting state to establish the correspondence between membrane voltage dynamics and fMRI for resting state functional connectivity networks. In Aim 2 I will train these mice to perform a sensorimotor task. I will image them during task training to assess changes in FC due to learning. I hypothesize that the correlation between fMRI BOLD and neural activity will be regionally specific for both resting state and task training, the latter will result in a measurable strengthening of FC between task-relevant areas. Completion of these aims will determine how functional networks observed with BOLD relate to neural activity and will provide insights into how FC reflects behaviorally relevant changes in the learning of a sensorimotor task. This results in a sharper understanding of the properties of neural network activity, its dependencies, and how to harness it in future fMRI studies.