BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

中文翻译：

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穹窿的频率依赖性电刺激优先影响中脑边缘多巴胺系统或前额叶皮层

背景菌毛/穹窿纤维系统是海马-VTA 环的重要组成部分，因此通过该纤维系统传播的活动控制中脑边缘多巴胺系统的活动。目标/假设我们假设用越来越多的电脉冲刺激伞毛/穹窿会导致中脑边缘多巴胺系统的活动增加，这与中脑边缘多巴胺能系统目标区域中神经元活动的同时变化相吻合。方法 用不同的脉冲协议对右侧的伞毛/穹窿纤维进行电刺激。刺激诱导的神经元活动变化通过 BOLD-fMRI 可视化，而刺激诱导的多巴胺释放，如测量中脑边缘多巴胺系统的活动，用体内快速扫描循环伏安法在伏隔核中测定。结果 根据协议，电菌毛/穹窿刺激在中脑边缘多巴胺系统的各种目标中引起了大胆的反应。低 theta 频率范围 (5 Hz) 的刺激主要在海马结构、边缘下皮层和隔膜中触发了显着的 BOLD 反应。β 频率范围 (20 Hz) 中的刺激导致内侧前额叶皮层 (mPFC)、伏隔核、纹状体和 VTA 的额外激活。高伽马频率范围 (100 Hz) 的刺激导致海马体和 mPFC 的进一步激活。在 100 Hz 刺激期间 mPFC 的强烈激活不仅取决于脉冲数，还取决于频率。因此，与连续的 5 或 20 Hz 脉冲相比，5 或 20 个高频脉冲的短脉冲在 mPFC 中引起更强的激活。相比之下，与连续 5 或 20 Hz 脉冲刺激相比，高频爆发菌毛/穹窿刺激并没有进一步激活中脑边缘多巴胺系统。结论 BOLD 反应和多巴胺能系统的激活之间存在频率依赖性分离。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目标区域的 BOLD 反应，尤其是 mPFC。与连续的 5 或 20 Hz 脉冲刺激相比，高频爆发菌毛/穹窿刺激不会进一步激活中脑边缘多巴胺系统。结论 BOLD 反应和多巴胺能系统的激活之间存在频率依赖性分离。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目标区域的 BOLD 反应，尤其是 mPFC。与连续的 5 或 20 Hz 脉冲刺激相比，高频爆发菌毛/穹窿刺激不会进一步激活中脑边缘多巴胺系统。结论 BOLD 反应和多巴胺能系统的激活之间存在频率依赖性分离。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目标区域的 BOLD 反应，尤其是 mPFC。