Mechanisms underlying positive and negative BOLD in the striatum

项目概要 血氧水平依赖性功能磁共振成像（BOLD fMRI）广泛应用 作为研究大脑功能的非侵入性技术。它的运作前提是脑血流量 在已知的过程中，通过增加神经元活动来更新大脑区域的能量底物供应 作为神经血管耦合。我们小组和其他人的积累结果表明，传统的 神经血管耦合可能不适用于纹状体，并且很可能是非典型的血管活性神经传递 在这个大脑区域中一直发挥着很大程度上未被解释的作用。纹状体是认知的重要枢纽， 动机、奖励和感觉运动功能，并了解其异常的血流动力学活动将提供 这些研究领域的重要背景。我们提出了两个中心假设： 纹状体是通过多巴胺释放介导的，而不是局部神经元活动，并且负 BOLD 在 纹状体由局部神经元激活诱导并通过其下游血管收缩介导 神经传递。我们将使用 3 种神经调节方法，包括光遗传学、化学遗传学和 药理学，以及 4 种记录技术，包括功能磁共振成像、电生理学、快速扫描循环 伏安法和光纤光度法来操纵和获取 BOLD、多巴胺释放、 和纹状体中的神经元活动。我们希望我们的结果能够为 BOLD 机制提供新的见解， 为不服从皮层下大脑区域的功能磁共振成像数据的准确解释奠定基础 传统的神经血管耦合规则。 1

PROJECT SUMMARY Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) is widely used as a non-invasive technique to study brain function. It operates based on the premise that cerebral blood flow renews the supply of energetic substrates to brain regions with increased neuronal activity in a process known as neurovascular coupling. Accumulating results from our group and others indicate that conventional neurovascular coupling may not apply to the striatum and is likely that atypical vasoactive neurotransmission has been playing a largely unaccounted role in this brain area. The striatum is a critical hub for cognition, motivation, reward, and sensorimotor function, and understanding its aberrant hemodynamic activity will provide crucial context to these fields of research. We have developed two central hypotheses: that positive BOLD in the striatum is mediated through dopamine release but not local neuronal activity, and that negative BOLD in the striatum is induced by local neuronal activation and mediated through their downstream vasoconstrictive neurotransmission. We will use 3 neural modulation approaches, including optogenetics, chemogenetics, and pharmacology, together with 4 recording technologies, including fMRI, electrophysiology, fast-scan cyclic voltammetry, and optical fiber-photometry to manipulate and acquire the changes in BOLD, dopamine release, and neuronal activity in the striatum. We expect our results to provide novel insights into BOLD mechanisms, and lay the foundation for accurate fMRI data interpretation in subcortical brain areas that do not obey the traditional neurovascular coupling rules. 1