Department of Psychology, University of Cambridge, Cambridge, UK.
Behavioral and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
Cereb Cortex. 2020 Mar 14;30(3):1016-1029. doi: 10.1093/cercor/bhz144.
Much evidence suggests that reversal learning is mediated by cortico-striatal circuitries with the orbitofrontal cortex (OFC) playing a prominent role. The OFC is a functionally heterogeneous region, but potential differential roles of lateral (lOFC) and medial (mOFC) portions in visual reversal learning have yet to be determined. We investigated the effects of pharmacological inactivation of mOFC and lOFC on a deterministic serial visual reversal learning task for rats. For reference, we also targeted other areas previously implicated in reversal learning: prelimbic (PrL) and infralimbic (IL) prefrontal cortex, and basolateral amygdala (BLA). Inactivating mOFC and lOFC produced opposite effects; lOFC impairing, and mOFC improving, performance in the early, perseverative phase specifically. Additionally, mOFC inactivation enhanced negative feedback sensitivity, while lOFC inactivation diminished feedback sensitivity in general. mOFC and lOFC inactivation also affected novel visual discrimination learning differently; lOFC inactivation paradoxically improved learning, and mOFC inactivation had no effect. We also observed dissociable roles of the OFC and the IL/PrL. Whereas the OFC inactivation affected only perseveration, IL/PrL inactivation improved learning overall. BLA inactivation did not affect perseveration, but improved the late phase of reversal learning. These results support opponent roles of the rodent mOFC and lOFC in deterministic visual reversal learning.
大量证据表明，反转学习是由皮质纹状体回路介导的，其中额眶回（OFC）起着突出的作用。OFC 是一个功能上异质的区域，但 lateral (lOFC) 和 medial (mOFC) 部分在视觉反转学习中的潜在差异作用尚未确定。我们研究了药理学失活 mOFC 和 lOFC 对大鼠确定性序列视觉反转学习任务的影响。作为参考，我们还针对先前涉及反转学习的其他区域：额前皮质的 prelimbic (PrL) 和 infralimbic (IL) 以及基底外侧杏仁核 (BLA)。失活 mOFC 和 lOFC 产生了相反的效果；lOFC 损害了早期、持续阶段的表现，而 mOFC 改善了这一表现。此外，mOFC 失活增强了负反馈敏感性，而 lOFC 失活则普遍降低了反馈敏感性。mOFC 和 lOFC 失活对新的视觉辨别学习的影响也不同；lOFC 失活反常地改善了学习，而 mOFC 失活则没有影响。我们还观察到 OFC 和 IL/PrL 的分离作用。OFC 失活仅影响持续，而 IL/PrL 失活则总体上改善了学习。BLA 失活不影响持续，但改善了反转学习的后期阶段。这些结果支持啮齿动物 mOFC 和 lOFC 在确定性视觉反转学习中的对立作用。
