Helbing Cornelia, Brocka Marta, Arboit Alberto, Lippert Michael T, Angenstein Frank
Functional Neuroimaging Group, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Magdeburg, Germany.
Center for Behavioral Brain Sciences (CBBS), Otto von Guericke University, Magdeburg, Germany.
Imaging Neurosci (Camb). 2024 Jun 21;2. doi: 10.1162/imag_a_00200. eCollection 2024.
To investigate the effect of endogenously released dopamine on the stimulus-induced blood oxygen level-dependent (BOLD) responses, we used rats expressing inhibitory designer receptors exclusively activated by designer drugs (DREADDs) in neurons of the ventral tegmental area (VTA) and electrically stimulated the fimbria/fornix. This stimulation activates multiple components of the mesolimbic dopamine system, as demonstrated by the BOLD signal changes during functional magnetic resonance imaging (fMRI) and dopamine release in the nucleus accumbens (NAcc) as detected byfast-scan cyclic voltammetry. Activation of inhibitory DREADDs by clozapine-oxide (CNO) significantly reduced stimulus-induced dopamine release and the BOLD response in the NAcc. In contrast, the concurrently induced BOLD response in the medial prefrontal cortex (mPFC) was not significantly reduced after CNO administration, but the hemodynamic response was shifted to the left. Specifically, the Granger causality test showed that the temporal relationship between the BOLD signal changes in the hippocampus and the mPFC, changed. Under control conditions (i.e., in the absence of CNO), the BOLD signal changes in the mPFC and NAcc clearly preceded the BOLD signal changes in the right hippocampus, whereas in the presence of CNO this was only the case for the BOLD signal changes in the NAcc. In the control rats, that is, the rats that received a control virus and thus did not express DREADDs in the VTA, this CNO-mediated effect was not present. Our results indicate that activation of the endogenous dopaminergic system has region-specific effects on the stimulus-induced BOLD responses, so there is no generally applicable fMRI parameter that clearly indicates increased activity of the dopaminergic system.
为了研究内源性释放的多巴胺对刺激诱导的血氧水平依赖（BOLD）反应的影响，我们使用了在腹侧被盖区（VTA）神经元中表达仅由设计药物激活的抑制性设计受体（DREADDs）的大鼠，并对穹窿/穹窿海马伞进行电刺激。如功能磁共振成像（fMRI）期间的BOLD信号变化以及通过快速扫描循环伏安法检测到的伏隔核（NAcc）中的多巴胺释放所示，这种刺激激活了中脑边缘多巴胺系统的多个组成部分。用氧化氯氮平（CNO）激活抑制性DREADDs可显著降低刺激诱导的多巴胺释放以及NAcc中的BOLD反应。相比之下，CNO给药后内侧前额叶皮质（mPFC）中同时诱导的BOLD反应没有显著降低，但血流动力学反应向左偏移。具体而言，格兰杰因果关系检验表明，海马体和mPFC中BOLD信号变化之间的时间关系发生了变化。在对照条件下（即不存在CNO），mPFC和NAcc中的BOLD信号变化明显先于右侧海马体中的BOLD信号变化，而在存在CNO的情况下，只有NAcc中的BOLD信号变化是这种情况。在对照大鼠中，即接受对照病毒且因此在VTA中不表达DREADDs的大鼠，不存在这种CNO介导的效应。我们的结果表明，内源性多巴胺能系统的激活对刺激诱导的BOLD反应具有区域特异性影响，因此不存在能明确表明多巴胺能系统活性增加的普遍适用的fMRI参数。
