Unité Neurobiologie Intégrative des Systèmes Cholinergiques, CNRS URA 2182, Institut Pasteur, Paris, France.
FASEB J. 2011 Jul;25(7):2145-55. doi: 10.1096/fj.10-178558. Epub 2011 Mar 14.
Social behavior is a defining mammalian feature that integrates emotional and motivational processes with external rewarding stimuli. It is thus an appropriate readout for complex behaviors, yet its neuronal and molecular bases remain poorly understood. In this study, we investigated the role of the mouse prefrontal area, particularly the involvement of β2-subunit nicotinic receptors (β2*-nAChRs) in a paradigm of social behavior with concurrent motivations. We previously observed that mice lacking β2*-nAChRs (β2(-/-)) display increased time in social contact and exaggerated approach movements toward the novel conspecific. Here, combining behavioral analysis, localized brain lesions, and lentiviral gene rescue, we found that c-Fos expression is specifically activated in the prelimbic (PrL) area of the prefrontal cortex (PFC) of mice exposed to a novel conspecific; lesions of the PrL area in wild-type mice produce the same social pattern as in β2(-/-) mice; and virally mediated reexpression of the β2-subunit in the PrL area of β2(-/-) mice rescues behavioral components in the social interaction task up to normal levels. Together, these data reveal that social interactions particularly mobilize the PrL area of the mouse PFC and that the presence of functional PrL β2*-nAChRs is necessary for this integrated behavior to emerge.
社会行为是哺乳动物的一个重要特征，它将情感和动机过程与外部奖励刺激结合在一起。因此，它是复杂行为的一个合适的指标，但它的神经元和分子基础仍知之甚少。在这项研究中，我们研究了小鼠前额叶区域的作用，特别是β2-亚单位烟碱型乙酰胆碱受体（β2*-nAChRs）在同时存在动机的社会行为范式中的作用。我们之前观察到，缺乏β2*-nAChRs（β2(-/-)）的小鼠表现出更多的社交接触时间，并对新的同种动物表现出过度的接近运动。在这里，我们结合行为分析、局部脑损伤和慢病毒基因拯救，发现 c-Fos 表达在暴露于新同种动物的小鼠前额叶皮层（PFC）的前扣带皮层（PrL）区域特异性激活；野生型小鼠的 PrL 区域损伤会产生与β2(-/-)小鼠相同的社交模式；并且β2(-/-)小鼠 PrL 区域β2-亚基的病毒介导再表达可将社交互动任务中的行为成分恢复到正常水平。这些数据共同揭示了社会互动特别动员了小鼠 PFC 的 PrL 区域，并且功能性 PrLβ2*-nAChRs 的存在对于这种综合行为的出现是必要的。
