The anterior cingulate area (ACC) is an integral part of the prefrontal cortex in mice and supports cognitive functions, including attentional processes, motion planning and execution as well as remote memory, fear and pain. Previous anatomical and functional imaging studies demonstrated that the ACC is interconnected with numerous brain regions, such as motor and sensory cortices, amygdala and limbic areas, suggesting it serves as a hub in functional networks. However, the exact role of the ACC in regulating functional network activity and connectivity remains to be elucidated. Recently developed neuromodulatory techniques, such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) allow for precise control of neuronal activity. In this study, we used an inhibitory kappa-opioid receptor DREADD (KORD) to temporally inhibit neuronal firing in the right ACC of mice and assessed functional network activity and connectivity using non-invasive functional magnetic resonance imaging (MRI). We demonstrated that KORD-induced inhibition of the right ACC induced blood oxygenation-level dependent (BOLD) signal decreases and increases in connected brain regions of both hemispheres. More specifically, altered neuronal activity could be observed in functional brain networks including connections with sensory cortex, thalamus, basolateral amygdala and ventral pallidum, areas involved in attention processes, working memory, fear behavior and reward respectively. Furthermore, these modulations in neuronal activity were associated with decreased intra- and interhemispheric functional connectivity. Our results consolidate the hub role of the mouse ACC in functional networks and further demonstrate that the combination of the DREADD technology and non-invasive functional imaging methods is a valuable tool for unraveling mechanisms of network function and dysfunction by reversible inactivation of selected targets.

中文翻译：

---

小鼠前扣带回区神经元的化学遗传沉默调节神经元活动和功能连接

前扣带回区 (ACC) 是小鼠前额叶皮层的一个组成部分，支持认知功能，包括注意力过程、运动规划和执行以及远程记忆、恐惧和疼痛。先前的解剖和功能成像研究表明，ACC 与许多大脑区域相互关联，例如运动和感觉皮层、杏仁核和边缘区域，表明它是功能网络的枢纽。然而，ACC 在调节功能网络活动和连接方面的确切作用仍有待阐明。最近开发的神经调节技术，例如由设计师药物 (DREADD) 独家激活的设计师受体，可以精确控制神经元活动。在这项研究中，我们使用抑制性 kappa-阿片受体 DREADD (KORD) 暂时抑制小鼠右侧 ACC 中的神经元放电，并使用非侵入性功能磁共振成像 (MRI) 评估功能网络活动和连接性。我们证明了右侧 ACC 诱导的血氧水平依赖性 (BOLD) 信号的 KORD 诱导抑制在两个半球的连接大脑区域中减少和增加。更具体地说，可以在功能性大脑网络中观察到神经元活动的改变，包括与感觉皮层、丘脑、基底外侧杏仁核和腹侧苍白球的连接，分别涉及注意力过程、工作记忆、恐惧行为和奖励的区域。此外，这些神经元活动的调节与半球内和半球间功能连接的减少有关。