Neurovascular coupling during spontaneous and sensory evoked activity

描述(申请人提供)：通过功能磁共振成像(FMRI)，自发和感觉诱发的脑血流变化被广泛用于推断大脑中的神经活动。然而，这些血流动力学变化与神经活动的关系、神经活动控制血流的途径以及感觉诱发和自发活动之间的相互作用仍然知之甚少。为了解决这些问题，我们将使用双光子激光扫描显微镜(2PLSM)和本征光学信号(IOS)来测量清醒、头部固定的小鼠躯体感觉皮质中自发和感觉诱发的血流动力学。我们将测量感觉诱发和自发神经活动与随后的血流量(神经血管耦合)之间的关系。通过测量血管或皮质神经元上缺乏M胆碱能受体的转基因小鼠的神经活动和血流量，将剖析这种偶联的信号通路。这将允许我们解开直接的血管扩张剂 乙酰胆碱通过增加神经兴奋性而产生的间接效应。最后，我们将确定感觉诱发活动如何与大脑中正在进行的自发活动相互作用。量化自发和感觉诱发的神经活动如何与血液流动相结合，对于了解健康大脑的功能至关重要。

DESCRIPTION (provided by applicant): Changes in spontaneous and sensory evoked cerebral blood flow are extensively used to infer neural activity in the brain with functional magnetic resonance imaging (fMRI). However, the relationship of these hemodynamic changes to neural activity, the pathways by which neural activity controls blood flow, and the interaction between sensory-evoked and spontaneous activity are still poorly understood. To address these questions, we will use 2-photon laser-scanning microscopy (2PLSM) and intrinsic optical signal (IOS) to measure spontaneous and sensory evoked hemodynamics in the somatosensory cortex of awake, head-fixed mice. We will measure the relationship between both sensory evoked and spontaneous neural activity and the subsequent blood flow ('neurovascular coupling'). The signaling pathways that underlying this coupling will be dissected by measuring neural activity and blood flow in transgenic mice lacking muscarinic cholinergic receptors on either blood vessels or cortical neurons. This will allow us to disentangle the direct vasodilatory effects of acetylcholine from the indirect effects mediated via increases in neural excitability. Finally, we will determine how sensory evoked activity interacts with ongoing spontaneous activity in the brain. Quantifying how spontaneous and sensory-evoked neural activity couples to blood flow is critical for understanding the function of the healthy brain.