More is less: a disinhibited prefrontal cortex impairs cognitive flexibility.
More is less: a disinhibited prefrontal cortex impairs cognitive flexibility.
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DOI：
10.1523/jneurosci.4623-10.2010
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发表时间：
2010-12-15
期刊：
影响因子：
--
通讯作者：
O'Donnell P
中科院分区：
文献类型：
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作者：
Gruber AJ;Calhoon GG;Shusterman I;Schoenbaum G;Roesch MR;O'Donnell P
前额叶皮质(PFC)对决策至关重要，在许多神经精神障碍中会出现功能障碍。对精神分裂症患者和相关动物模型的研究表明，PFC抑制中间神经元功能丧失。例如，患有新生大鼠腹侧海马损伤(NVHL)的大鼠表现出多巴胺(DA)对PFC中间神经元的调制不足。PFC是否在这个模型中变得不受约束并改变决策仍有待确定。在这里，我们记录了NVHL大鼠在奖励-折扣选择任务中激活DA系统的内侧PFC的神经活动。老鼠被训练对气味进行采样，这些气味指示它们在两个喂食器中选择一个，这些喂食器提供的液体量不同。在NVHL大鼠，PFC内可能的锥体神经元过度活跃，而任务相关的场电位振荡显著减少，这与气味采样过程中DA对神经元间激活的损害导致处理过程紊乱一致。通过检查反应偏差和逆转奖励结果后的错误来测试认知灵活性。与对照组相比，NVHL大鼠表现出灵活性受损，因为它们跟踪奖励结果的变化的能力较差，并犯下更多的反应错误。代谢型谷氨酸受体2/3激动剂LY379268(1 mg/kg，i.p.)降低皮质兴奋性改善了NVHL大鼠的行为灵活性，但不能改善对照组。此外，拮抗剂乙氯必利(0.02 mg/kg，i.p.)还参与了D2多巴胺受体。降低了只能控制动物的能力。我们得出结论，NVHL大鼠存在PFC去抑制，影响神经信息处理和适当行为反应的选择。
The prefrontal cortex (PFC) is critical for decision making, and it becomes dysfunctional in many neuropsychiatric disorders. Studies in schizophrenia patients and relevant animal models suggest loss of PFC inhibitory interneuron function. For instance, rats with a neonatal ventral hippocampal lesion (NVHL) show a deficient modulation of PFC interneurons by dopamine (DA). Whether the PFC becomes disinhibited in this model and alters decision-making remains to be determined. Here, we recorded neural activity in the medial PFC of NVHL rats during a reward-discounting choice task that activates DA systems. Rats were trained to sample odors that instructed them to select one of two feeders that delivered unequal amounts of liquid. Putative pyramidal neurons in the PFC were hyperactive while task-related field potential oscillations were significantly reduced in NVHL rats, consistent with impaired interneuron activation by DA during odor sampling leading to disorganized processing. Cognitive flexibility was tested by examining response bias and errors after reversing reward outcomes. NVHL rats demonstrated impaired flexibility as they were less able to track changes in reward outcome and made more response errors than controls. Reducing cortical excitability with the metabotropic glutamate receptor 2/3 agonist LY379268 (1 mg/kg, i.p.) improved behavioral flexibility in NVHL rats but not controls. Furthermore, D2 dopamine receptors were involved, as the antagonist eticlopride (0.02 mg/kg, i.p.) reduced the ability to switch in only control animals. We conclude that NVHL rats present PFC disinhibition, which affects neural information processing and the selection of appropriate behavioral responses.