A Functional Gradient in the Rodent Prefrontal Cortex Supports Behavioral Inhibition
A Functional Gradient in the Rodent Prefrontal Cortex Supports Behavioral Inhibition
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DOI：
10.1016/j.cub.2016.12.052
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发表时间：
2017-02-20
期刊：
影响因子：
9.2
通讯作者：
Diester, Ilka
中科院分区：
文献类型：
--
作者：
Hardung, Stefanie;Epple, Robert;Diester, Ilka
计划和执行对外部刺激的适当时间反应的能力是建立在运动启动和抑制之间精心安排的平衡基础上的。在涉及前额叶皮质（PFC）[1]的冲动控制障碍中，这种平衡被扰乱，强调了PFC在适当定时动作中发挥的关键作用[2-4]。本研究采用光遗传学和电生理技术系统分析了大鼠内侧PFC （mPFC）和眶额皮质（OFC）的五个关键亚区在动作控制中的功能作用[5-9]。mPFC亚区失活引起了表现的剧烈变化，即过早反应的增加（前边缘皮质，PL）或减少（下边缘皮质，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。相反，OFC亚区（主要是腹侧OFC，即VO）的抑制显著损害了外部线索后快速反应的能力。与这些发现一致的是，在反应准备期间，mPFC的活性比OFC的活性更能预测试验结果和反应时间。这些数据支持了IL和PL在指导主动行为中相反作用的概念，并论证了OFC主要参与反应性运动控制。通过赋予啮齿动物PFC部分明确的作用，本研究有助于更深入地了解该脑区域的功能异质性，从而可以指导在这种神经疾病动物模型中PFC相关冲动控制障碍的医学相关研究[10-12]。
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 electro-physiological 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].