Functional Neuroimaging Group, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Otto von Guericke University, Magdeburg, Germany.
Functional Neuroimaging Group, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Otto von Guericke University, Magdeburg, Germany; Leibniz Institute for Neurobiology (LIN), Magdeburg, Germany; Medical Faculty, Otto von Guericke University, Magdeburg, Germany.
Brain Stimul. 2020 May-Jun;13(3):753-764. doi: 10.1016/j.brs.2020.02.026. Epub 2020 Feb 26.
The fimbria/fornix fiber system is an essential part of the hippocampal-VTA loop, and therefore activities that are propagated through this fiber system control the activity of the mesolimbic dopamine system.
OBJECTIVES/HYPOTHESIS: We hypothesized that stimulation of the fimbria/fornix with an increasing number of electrical pulses would cause increasing activity of the mesolimbic dopamine system, which coincides with concurrent changes in neuronal activities in target regions of the mesolimbic dopaminergic system.
Right fimbria/fornix fibers were electrically stimulated with different pulse protocols. Stimulus-induced changes in neuronal activities were visualized with BOLD-fMRI, whereas stimulus-induced release of dopamine, as measured for the activity of the mesolimbic dopamine system, was determined in the nucleus accumbens with in vivo fast-scan cyclic voltammetry.
Dependent on the protocol, electrical fimbria/fornix stimulation caused BOLD responses in various targets of the mesolimbic dopamine system. Stimulation in the low theta frequency range (5 Hz) triggered significant BOLD responses mainly in the hippocampal formation, infralimbic cortex, and septum. Stimulation in the beta frequency range (20 Hz) caused additional activation in the medial prefrontal cortex (mPFC), nucleus accumbens, striatum, and VTA. Stimulation in the high-gamma frequency range (100 Hz) caused further activation in the hippocampus proper and mPFC. The strong activation in the mPFC during 100 Hz stimulations depended not only on the number of pulses but also on the frequency. Thus, short bursts of 5 or 20 high-frequency pulses caused stronger activation in the mPFC than continuous 5 or 20 Hz pulses. In contrast, high-frequency burst fimbria/fornix stimulation did not further activate the mesolimbic dopamine system when compared to continuous 5 or 20 Hz pulse stimulation.
There exists a frequency-dependent dissociation between BOLD responses and activation of the dopaminergic system. Low frequencies were more efficient to activate the mesolimbic dopamine system, whereas high frequencies were more efficient to trigger BOLD responses in target regions of the mesolimbic dopamine system, particularly the mPFC.
穹窿/海马伞纤维系统是海马体-VTA 回路的重要组成部分，因此通过该纤维系统传播的活动控制着中脑边缘多巴胺系统的活动。
目的/假设：我们假设，用越来越多的电脉冲刺激穹窿/海马伞会引起中脑边缘多巴胺系统活动的增加，这与中脑边缘多巴胺能系统靶区神经元活动的同时变化相一致。
用不同的脉冲方案刺激右侧穹窿/海马伞纤维。用 BOLD-fMRI 显示刺激引起的神经元活动变化，而用原位快速扫描循环伏安法在伏隔核中测量刺激引起的多巴胺释放，作为中脑边缘多巴胺系统活动的指标。
根据方案的不同，电刺激穹窿/海马伞引起中脑边缘多巴胺系统的各种靶区的 BOLD 反应。在低频 theta 范围（5Hz）刺激引起主要在海马结构、边缘下皮质和隔区的显著 BOLD 反应。在 beta 频率范围（20Hz）刺激引起内侧前额叶皮质（mPFC）、伏隔核、纹状体和 VTA 的额外激活。在高频 gamma 范围（100Hz）刺激引起海马体本身和 mPFC 的进一步激活。在 100Hz 刺激时 mPFC 的强烈激活不仅取决于脉冲的数量，而且取决于频率。因此，5 或 20 个高频脉冲的短爆发比连续的 5 或 20Hz 脉冲引起更强的 mPFC 激活。相比之下，与连续的 5 或 20Hz 脉冲刺激相比，高频爆发刺激穹窿/海马伞并没有进一步激活中脑边缘多巴胺系统。
在 BOLD 反应和多巴胺能系统激活之间存在一种频率依赖性的分离。低频更有效地激活中脑边缘多巴胺系统，而高频更有效地触发中脑边缘多巴胺系统靶区的 BOLD 反应，特别是 mPFC。
