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（FC）已被发现在广泛的其他难以区分的疾病中发生改变。 states.非侵入性研究全脑FC网络组织的最常用工具是功能性的 磁共振成像（fMRI）。功能磁共振成像依赖于一种间接的和不加选择的活动测量， 血氧水平依赖性（BOLD）对比机制。通过捕捉BOLD信号的波动 fMRI可以检测休息时或表演过程中大脑区域之间的远程同步 具体任务。这些区域被推断为在功能上是相连的，并被认为涉及同步性。 通过可塑性连接在一起的共同功能的神经元群体。解释 从BOLD fMRI研究中获得的FC网络的研究目前受到以下限制：1）fMRI BOLD信号的依赖性 血流动力学变化作为神经活动的代表，2）对机制基础的理解有限 在行为相关纵向重组的背景下，我的长期目标是更好地 了解BOLD与行为相关多区域回路中神经活动之间的关系， 先进的大脑网络分析。一旦我们知道血管和神经的变化如何影响FC， 对于网络功能障碍，可以利用fMRI提供更强大的基于fMRI的疾病检测。 在这个提议的项目中，我将使用表达一种新的JEDI-1 P电压荧光蛋白的EMX 1-Cre小鼠， 背侧皮层的兴奋性神经元这个电压传感器有一个很大的光谱带，允许我们记录 慢的亚阈值电压活动和快的伽马带活动。宽视场光学成像将是 结合fMRI将FC中的神经元变化与fMRI测量的血流动力学变化联系起来。目标1 I 将在静息状态下对这些JEDI-1 P进行成像，以建立膜电压动态之间的对应关系， 和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 感觉运动任务我将在任务训练期间对他们进行成像，以评估FC因学习而发生的变化。我假设 fMRI BOLD和神经活动之间的相关性对于静息状态和 任务培训，后者将导致可衡量的加强FC之间的任务相关领域。完成 这些目标将确定如何与BOLD观察到的功能网络与神经活动相关，并将提供 深入了解FC如何反映感觉运动任务学习中的行为相关变化。这导致 更深刻地理解神经网络活动的属性，其依赖关系，以及如何利用它， 未来的功能磁共振成像研究

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.