A multimodal approach to understanding the development of neurovascular coupling

摘要：血流动力学信号使我们能够非侵入性地检测神经活动，并可以为 对出生后发育过程中的神经变化有很好的洞察力。然而，人们对它的理解并不清楚 神经活动与新生儿和青少年血流量和氧合变化的关系 大脑。之前对麻醉动物和镇静人类的研究得出了相互矛盾的结果。 至于神经血管偶联的标志和大小，这个悬而未决的问题阻碍了它的使用 婴儿和儿童的血流动力学成像。在这份提案中，我们将确定如何 体感皮层神经血管偶联在出生后发育过程中的变化 觉醒的小鼠大脑，神经血管偶联的变化如何影响大胆的fMRI信号，以及如何 行为状态可以改变神经血管耦合。我们将使用多模式方法，结合 光学成像(本征光学信号成像和双光子显微镜)、电生理学和 FMRI从单个水平阐明血流动力学信号与神经活动的关系 血管通达整个大脑。我们将机械地剖析局部神经活动和 心血管对血流动力学信号的影响。这里提出的研究将使使用 血流动力学成像研究婴儿的神经活动、可塑性和神经发育障碍 以及幼年的人类和动物。

Abstract: Hemodynamic signals allow us to non-invasively assay neural activity and could provide great insight into neural changes during postnatal development. However, it is not clearly understood how neural activity is related to changes in blood flow and oxygenation in the neonatal and juvenile brain. Previous studies in anesthetized animals and sedated humans have come to conflicting results as to the sign and magnitude of neurovascular coupling, and this unresolved issue has stalled the use of hemodynamic imaging in infants and children. In this proposal, we will determine how neurovascular coupling changes during postnatal development in the somatosensory cortex of the awake mouse brain, how this change in neurovascular coupling impacts BOLD fMRI signals, and how behavioral state can alter neurovascular coupling. We will use a multimodal approach, combining optical imaging (intrinsic optical signal imaging and 2-photon microscopy), electrophysiology, and fMRI to elucidate the relationship of hemodynamic signals to neural activity from the levels of single vessels up to the whole brain. We will mechanistically dissect the roles of local neural activity and cardiovascular effects on hemodynamic signals. The research proposed here will enable the use of hemodynamic imaging to study neural activity, plasticity, and neurodevelopmental disorders in infants and juvenile humans and animals.