Abstract：
The forkhead box protein P2 (Foxp2), initially identified for its role in speech and language development, plays an important role in neural development. Previous studies investigated the function of the Foxp2 gene by deleting or mutating Foxp2 from developmental stages. Little is known about its physiological function in adult brains. Although Foxp2 has been well studied in the dorsal striatum, its function in the nucleus accumbens (NAc) of the ventral striatum remains elusive. Here, we examine the physiological function of Foxp2 in NAc of mouse brains. We conditionally knocked out Foxp2 by microinjections of AAV-EGFP-Cre viruses into the medial shell of NAc of Foxp2 floxed (cKO) mice. Immunostaining showed increased c-Fos positive cells in cKO NAc at basal levels, suggesting an abnormality in Foxp2-deficient NAc cells. Unbiased behavioral profiling of Foxp2 cKO mice showed abnormalities in limbic-associated function. Foxp2 cKO mice exhibited abnormal social novelty without preference for interaction with strangers and familiar mice. In appetitive reward learning, Foxp2 cKO mice failed to learn the time expectancy of food delivery. In fear learning, Foxp2 cKO mice exhibited abnormal increases in freezing levels in response to tone paired with foot shock during fear conditioning. The extinction of the fear response was also altered in Foxp2 cKO mice. In contrast, conditional knockout of Foxp2 in NAc did not affect locomotion, motor coordination, thermal pain sensation, anxiety- and depression-like behaviors. Collectively, our study suggests that Foxp2 has a multifaceted physiological role in NAc in the regulation of limbic function in the adult brain.
摘要：
叉头盒蛋白P2（Foxp2），最初确定它在言语和语言发展中的作用，在神经发育中起着重要作用。先前的研究通过从发育阶段删除或突变Foxp2来研究Foxp2基因的功能。人们对它在成人大脑中的生理功能知之甚少。尽管Foxp2已经在背侧纹状体中得到了很好的研究，它在腹侧纹状体的伏隔核（NAc）中的功能仍然难以捉摸。这里,我们研究了Foxp2在小鼠大脑NAc中的生理功能。我们通过将AAV-EGFP-Cre病毒显微注射到Foxp2floxed（cKO）小鼠的NAc的内侧壳中来有条件地敲除Foxp2。免疫染色显示cKONAc中c-Fos阳性细胞在基础水平增加，提示Foxp2缺陷的NAc细胞异常。Foxp2cKO小鼠的无偏行为谱分析显示边缘相关功能异常。Foxp2cKO小鼠表现出异常的社交新颖性，而不喜欢与陌生人和熟悉的小鼠互动。在食欲奖励学习中，Foxp2cKO小鼠未能学习食物递送的预期时间。在恐惧学习中，Foxp2cKO小鼠在恐惧调节过程中响应于与足部休克配对的语气而表现出冻结水平的异常增加。在Foxp2cKO小鼠中，恐惧反应的消失也发生了变化。相比之下,NAc中Foxp2的条件敲除不影响运动，电机协调，热疼痛感觉，焦虑和抑郁的行为。总的来说，我们的研究表明，Foxp2在NAc中具有多方面的生理作用，调节成人大脑的边缘功能。
