Park Eun Hye, O'Reilly Sparks Kally C, Grubbs Griffin, Taborga David, Nicholas Kyndall, Ahmed Armaan S, Ruiz-Péreza Natalie, Kim Natalie, Segura-Carrillo Simon, Fenton André A
Center for Neural Science, New York University, New York, United States.
Psychiatry, Columbia University Irving Medical Center, New York State Psychiatric Institute, New York, United States.
Elife. 2025 Jun 23;13:RP104475. doi: 10.7554/eLife.104475.
Cognitive control tasks require using one class of information while ignoring competing classes of information. The central role of the medial prefrontal cortex (mPFC) in cognitive control is well established in the primate literature and largely accepted in the rodent literature because mPFC damage causes deficits in tasks that may require cognitive control, as inferred, typically from the task design. In prior work, we used an active place avoidance task where a rat or mouse on a rotating arena is required to avoid the stationary task-relevant locations of a mild shock and ignore the rotating task-irrelevant locations of those shocks. The task is impaired by hippocampal manipulations, and the discharge of hippocampal place cell populations judiciously alternates between representing stationary locations near the shock zone and rotating locations far from the shock zone, demonstrating cognitive control concurrently in behavior and the hippocampal representation of spatial information. Here, we test whether rat mPFC lesion impairs the active place avoidance task to evaluate two competing hypotheses, a 'central-computation' hypothesis that the mPFC is essential for the computations required for cognitive control and an alternative 'local-computation' hypothesis that other brain areas can perform the computations required for cognitive control, independent of mPFC. Ibotenic acid lesion of the mPFC was effective, damaging the cingulate, prelimbic, and infralimbic cortices. The lesion also altered the normal coordination of metabolic activity across remaining structures. The lesion did not impair learning to avoid the initial location of shock or long-term place avoidance memory, but impaired avoidance after the shock was relocated. The lesion also did not impair the alternation between task-relevant and task-irrelevant hippocampal representations of place information. These findings support the local-computation hypothesis that computations required for cognitive control can occur locally in brain networks independently of the mPFC.
认知控制任务需要运用一类信息，同时忽略其他相互竞争的信息类别。内侧前额叶皮质（mPFC）在认知控制中的核心作用在灵长类动物文献中已得到充分证实，并且在啮齿动物文献中也基本被接受，因为mPFC损伤会导致在可能需要认知控制的任务中出现缺陷，通常是从任务设计推断得出的。在之前的研究中，我们使用了一种主动位置回避任务，即要求处于旋转场地的大鼠或小鼠避开与轻度电击相关的静止任务位置，并忽略那些电击的旋转任务无关位置。该任务会因海马体操作而受损，并且海马体位置细胞群的放电会在代表靠近电击区的静止位置和远离电击区的旋转位置之间明智地交替，这表明在行为和空间信息的海马体表征中同时存在认知控制。在这里，我们测试大鼠mPFC损伤是否会损害主动位置回避任务，以评估两种相互竞争的假设，一种是“中央计算”假设，即mPFC对于认知控制所需的计算至关重要；另一种是替代性的“局部计算”假设，即其他脑区可以独立于mPFC执行认知控制所需的计算。mPFC的鹅膏蕈氨酸损伤是有效的，损害了扣带回、前额叶和边缘下皮质。该损伤还改变了其余结构间代谢活动的正常协调。损伤并未损害学习避开电击的初始位置或长期位置回避记忆，但在电击重新定位后损害了回避行为。该损伤也未损害海马体对位置信息的任务相关和任务无关表征之间的交替。这些发现支持了局部计算假设，即认知控制所需的计算可以在脑网络中局部发生，独立于mPFC。
