Interneurons Are Necessary for Coordinated Activity During Reversal Learning in Orbitofrontal Cortex
Interneurons Are Necessary for Coordinated Activity During Reversal Learning in Orbitofrontal Cortex
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DOI：
10.1016/j.biopsych.2014.07.023
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发表时间：
2015-03-01
影响因子：
10.6
通讯作者：
Powell, Elizabeth M.
中科院分区：
文献类型：
--
作者：
Bissonette, Gregory B.;Schoenbaum, Geoffrey;Powell, Elizabeth M.
背景技术背景：大脑皮质γ-氨基丁酸能中间神经元功能障碍被假设为导致认知缺陷与人类神经精神疾病共病，包括精神分裂症，自闭症和癫痫。我们先前已经证明，与精神分裂症相关的Plaur基因突变的小鼠在额叶皮质小白蛋白表达中间神经元中存在缺陷。Plaur小鼠有受损的逆转学习，类似的赤字中观察到的精神分裂症patients.METHODS：我们研究了小白蛋白interneurons在眶额皮层逆转学习过程中的作用，通过记录单个单位的活动，从180个控制和224个Plaur小鼠神经元在一系列的逆转任务。结果：对照组小鼠神经元在辨别和逆转学习过程中均表现出较强的阶段性反应，且反应强度与行为表现相关。尽管Plaur小鼠的基线放电显著增强，但神经对正确或错误决策的选择性减少，与行为无关，奖励编码缩小。此外，Plaur小鼠表现出显着减少的神经元的数量，编码的预期结果跨任务阶段在decision periods.CONCLUSIONS：这些数据表明，parvalbumin interneurons是必要的眶额皮质的结果的代表。在关键决策过程中，抑制缺陷会减弱选择性神经放电，从而导致行为不稳定。这些数据为人类神经精神疾病（如自闭症、癫痫和精神分裂症）中伴随这些γ-氨基丁酸能中间神经元丢失的认知控制障碍提供了潜在的解释。
BACKGROUND: Cerebral cortical gamma-aminobutyric acidergic interneuron dysfunction is hypothesized to lead to cognitive deficits comorbid with human neuropsychiatric disorders, including schizophrenia, autism, and epilepsy. We have previously shown that mice that harbor mutations in the Plaur gene, which is associated with schizophrenia, have deficits in frontal cortical parvalbumin-expressing interneurons. Plaur mice have impaired reversal learning, similar to deficits observed in patients with schizophrenia.METHODS: We examined the role of parvalbumin interneurons in orbitofrontal cortex during reversal learning by recording single unit activity from 180 control and 224 Plaur mouse neurons during a serial reversal task. Neural activity was analyzed during correct and incorrect decision choices and reward receipt.RESULTS: Neurons in control mice exhibited strong phasic responses both during discrimination and reversal learning to decisions and rewards, and the strength of the response was correlated with behavioral performance. Although baseline firing was significantly enhanced in Plaur mice, neural selectivity for correct or erroneous decisions was diminished and not correlated with behavior, and reward encoding was downscaled. In addition, Plaur mice showed a significant reduction in the number of neurons that encoded expected outcomes across task phases during the decision period.CONCLUSIONS: These data indicate that parvalbumin interneurons are necessary for the representation of outcomes in orbitofrontal cortex. Deficits in inhibition blunt selective neural firing during key decisions, contributing to behavioral inflexibility. These data provide a potential explanation for disorders of cognitive control that accompany the loss of these gamma-aminobutyric acidergic interneurons in human neuropsychiatric disorders, such as autism, epilepsy, and schizophrenia.