Mechanisms underlying positive and negative BOLD in the striatum

项目总结 血氧水平依赖的功能磁共振成像(BOLD FMRI)被广泛应用 作为一种研究大脑功能的非侵入性技术。它的运作基于这样一个前提：脑血流 在一个已知的过程中，通过增加神经元活动来更新大脑区域的能量底物供应 神经血管耦合。我们小组和其他人的积累结果表明，常规 神经血管偶联可能不适用于纹状体，很可能是非典型的血管活性神经传递 一直在这个大脑区域扮演着一个很大程度上未被解释的角色。纹状体是认知的关键中枢， 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 这些研究领域的关键背景。我们提出了两个中心假设： 纹状体是通过多巴胺释放而不是局部神经元活动来调节的，而在 纹状体由局部神经元激活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，以及四项记录技术，包括功能磁共振成像、电生理、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、 以及纹状体中的神经元活动。我们希望我们的结果能为大胆的机制提供新的见解， 并为在皮质下不服从 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