Pittaras Elsa Cécile, Faure Alexis, Leray Xavier, Moraitopoulou Elina, Cressant Arnaud, Rabat Arnaud Alexandre, Meunier Claire, Fossier Philippe, Granon Sylvie
CNRS 9197, Institut de Neuroscience Paris Saclay, Orsay, France; Institut de Recherche Biomédicale des Armées et Unité Fatigue & Vigilance, Brétigny-sur-orge, France.
CNRS 9197, Institut de Neuroscience Paris Saclay , Orsay , France.
Front Psychiatry. 2016 Oct 14;7:171. doi: 10.3389/fpsyt.2016.00171. eCollection 2016.
Decision-making is an essential component of our everyday life commonly disabled in a myriad of psychiatric conditions, such as bipolar and impulsive control disorders, addiction and pathological gambling, or schizophrenia. A large cerebral network encompassing the prefrontal cortex, the amygdala, and the nucleus accumbens is activated for efficient decision-making.
We developed a mouse gambling task well suited to investigate the influence of uncertainty and risk in decision-making and the role of neurobiological circuits and their monoaminergic inputs. Neuronal nicotinic acetylcholine receptors (nAChRs) of the PFC are important for decision-making processes but their presumed roles in risk-taking and uncertainty management, as well as in cellular balance of excitation and inhibition (E/I) need to be investigated.
Using mice lacking nAChRs - β2 mice, we evidence for the first time the crucial role of nAChRs in the fine tuning of prefrontal E/I balance together with the PFC, insular, and hippocampal alterations in gambling behavior likely due to sensitivity to penalties and flexibility alterations. Risky behaviors and perseveration in extinction task were largely increased in β2 mice as compared to control mice, suggesting the important role of nAChRs in the ability to make appropriate choices adapted to the outcome.
决策是我们日常生活的重要组成部分，在多种精神疾病中通常会受到损害，如双相情感障碍和冲动控制障碍、成瘾和病态赌博，或精神分裂症。一个包含前额叶皮层、杏仁核和伏隔核的大型脑网络会被激活以实现高效决策。
我们开发了一种小鼠赌博任务，非常适合研究不确定性和风险对决策的影响以及神经生物学回路及其单胺能输入的作用。前额叶皮层的神经元烟碱型乙酰胆碱受体（nAChRs）对决策过程很重要，但它们在冒险和不确定性管理以及细胞兴奋与抑制平衡（E/I）中的假定作用需要进行研究。
使用缺乏nAChRs的小鼠——β2小鼠，我们首次证明了nAChRs在前额叶E/I平衡的微调中起着关键作用，同时还发现β2小鼠的赌博行为中前额叶皮层、岛叶和海马体发生了改变，这可能是由于对惩罚的敏感性和灵活性改变所致。与对照小鼠相比，β2小鼠在消退任务中的冒险行为和持续性显著增加，表明nAChRs在根据结果做出适当选择的能力中起着重要作用。
