Ernst Strüngmann Institute, Deutschordenstraße 46, 60579 Frankfurt/Main, Germany; Faculty of Biology, University of Freiburg, Albertstraße 23, 79104 Freiburg, Germany; BrainLinks-BrainTools, University of Freiburg, Georges-Köhler-Allee 079, 79110 Freiburg, Germany.
Faculty of Biology, University of Freiburg, Albertstraße 23, 79104 Freiburg, Germany; BIOTEC, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany.
Curr Biol. 2017 Feb 20;27(4):549-555. doi: 10.1016/j.cub.2016.12.052. Epub 2017 Feb 9.
The ability to plan and execute appropriately timed responses to external stimuli is based on a well-orchestrated balance between movement initiation and inhibition. In impulse control disorders involving the prefrontal cortex (PFC) [1], this balance is disturbed, emphasizing the critical role that PFC plays in appropriately timing actions [2-4]. Here, we employed optogenetic and electrophysiological techniques to systematically analyze the functional role of five key subareas of the rat medial PFC (mPFC) and orbitofrontal cortex (OFC) in action control [5-9]. Inactivation of mPFC subareas induced drastic changes in performance, namely an increase (prelimbic cortex, PL) or decrease (infralimbic cortex, IL) of premature responses. Additionally, electrophysiology revealed a significant decrease in neuronal activity of a PL subpopulation prior to premature responses. In contrast, inhibition of OFC subareas (mainly the ventral OFC, i.e., VO) significantly impaired the ability to respond rapidly after external cues. Consistent with these findings, mPFC activity during response preparation predicted trial outcomes and reaction times significantly better than OFC activity. These data support the concept of opposing roles of IL and PL in directing proactive behavior and argue for an involvement of OFC in predominantly reactive movement control. By attributing defined roles to rodent PFC sections, this study contributes to a deeper understanding of the functional heterogeneity of this brain area and thus may guide medically relevant studies of PFC-associated impulse control disorders in this animal model for neural disorders [10-12].
计划和执行对外界刺激的适时反应的能力基于运动启动和抑制之间的良好协调。在涉及前额叶皮层（PFC）的冲动控制障碍中[1]，这种平衡被打乱，强调了 PFC 在适当调整行为方面的关键作用[2-4]。在这里，我们采用光遗传学和电生理学技术，系统地分析了大鼠内侧前额叶皮层（mPFC）和眶额皮层（OFC）五个关键亚区在动作控制中的功能作用[5-9]。mPFC 亚区的失活导致行为表现发生剧烈变化，即过早反应增加（额前皮质，PL）或减少（边缘皮质，IL）。此外，电生理学显示，在过早反应之前，PL 亚群的神经元活动显著减少。相比之下，OFC 亚区的抑制（主要是腹侧 OFC，即 VO）显著损害了对外界线索快速反应的能力。与这些发现一致的是，mPFC 在反应准备期间的活动比 OFC 活动更能显著预测试验结果和反应时间。这些数据支持 IL 和 PL 在指导主动行为方面的对立作用的概念，并认为 OFC 参与了主要的反应性运动控制。通过为啮齿动物 PFC 部分赋予明确的作用，这项研究有助于更深入地了解该脑区的功能异质性，并可能指导该神经障碍动物模型中与 PFC 相关的冲动控制障碍的医学相关研究[10-12]。
