Selective ablation of VIP interneurons in the rodent prefrontal cortex results in increased impulsivity.

Selective ablation of VIP interneurons in the rodent prefrontal cortex results in increased impulsivity.
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DOI:
10.1371/journal.pone.0286209
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发表时间:
2023
期刊:
影响因子:
3.7
通讯作者:
--
中科院分区:
综合性期刊3区
文献类型:
--
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众所周知,追求新奇和冲动是导致心理障碍的重要风险因素,包括物质使用障碍和行为成瘾。虽然前额叶皮质的功能障碍是这些疾病的症结所在,但在细胞水平上,关于神经元活动的变化如何推动冲动和寻求新奇的变化,人们知之甚少。我们在雄性和雌性小鼠中都利用cre依赖的caspase-3消融来选择性地消融前额叶皮质中表达血管活性肠肽(VIP)的中间神经元,以更好地探索这一微电路在特定行为任务中的功能。在三种选择的系列反应时间测试中,半胱氨酸天冬氨酸酶损毁的动物在类似焦虑的行为或享乐食物摄入量方面没有变化,但在较长时间的试验中冲动反应特别增加。总之,这些数据表明了一种电路水平的机制,在这种机制中,VIP中间神经元起到了门的作用,在高期望期选择性地做出反应。
It has been well-established that novelty-seeking and impulsivity are significant risk factors for the development of psychological disorders, including substance use disorder and behavioral addictions. While dysfunction in the prefrontal cortex is at the crux of these disorders, little is known at the cellular level about how alterations in neuron activity can drive changes in impulsivity and novelty seeking. We harnessed a cre-dependent caspase-3 ablation in both male and female mice to selectively ablate vasoactive intestinal peptide (VIP)-expressing interneurons in the prefrontal cortex to better explore how this microcircuit functions during specific behavioral tasks. Caspase-ablated animals had no changes in anxiety-like behaviors or hedonic food intake but had a specific increase in impulsive responding during longer trials in the three-choice serial reaction time test. Together, these data suggest a circuit-level mechanism in which VIP interneurons function as a gate to selectively respond during periods of high expectation.
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