Imaging neurovascular coupling and functional connectivity in the behaving mouse

描述(申请人提供)：本项目的目标是量化自然行为如何调节大脑皮层的血流动力学信号，并测量它们与神经活动的耦合。我们将使用电生理学、内部光学信号成像和双光子激光扫描显微镜，同时测量清醒的头部固定小鼠的大脑皮质中的神经活动和血流动力学信号。老鼠将可以在球形跑步机上自由切换跑步、梳理或静止的行为。我们将利用药理学来剖析中枢神经和外周心血管机制在控制脑血流中的相对作用。定义神经活动和血流之间关系的神经血管脉冲反应函数将被量化，以测试神经血管耦合的稳定性。最后，我们将测试功能网络，即休息时血流相关的区域，在运动时是否也有类似的关联。了解行为状态是否以及如何调节皮质血流动力学反应，血流与神经活动的耦合，以及功能连接，对于解释血流动力学信号都是至关重要的。

DESCRIPTION (provided by applicant): The goal of this project is to quantify how natural behaviors modulate hemodynamic signals in the cortex, and to measure their coupling to neural activity. We will concurrently measure neural activity and hemodynamic signals, using electrophysiology, intrinsic optical signal imaging and two-photon laser scanning microscopy, in the cortex of awake, head-fixed mice. Mice will be free to alternate between running, grooming or quiescent behaviors on top of a spherical treadmill. We will use pharmacology to dissect the relative contributions of central neural and peripheral cardiovascular mechanisms in controlling cerebral blood flow. The neurovascular impulse response function, which defines the relationship between neural activity and blood flow, will be quantified across behaviors to test the constancy of neurovascular coupling. Lastly, we will test whether functional networks, areas with correlated blood flow during rest, are similarly correlated during locomotion. Understanding if, and how, the behavioral state modulates the cortical hemodynamic response, the coupling of blood flow to neural activity, and functional connectivity, are all critical for the interpretationof hemodynamic signals.