Department of Psychology and Neuroscience, Baylor University, Waco, TX, 76798, USA.
Institute of Biomedical Studies, Baylor University, Waco TX 76798, USA.
Behav Brain Res. 2020 Jan 27;378:112189. doi: 10.1016/j.bbr.2019.112189. Epub 2019 Oct 3.
The NS-Pten knockout (KO) mouse exhibits hyperactivity of the mammalian target of rapamycin (mTOR) and is a model of autism spectrum disorder (ASD). ASD presents with marked deficits in communication which can be elucidated by investigating their counterpart in mice, ultrasonic vocalizations (USVs). While USVs have been found to be altered in NS-Pten KO pups, no study has assessed whether this communication deficit persists into adulthood. In the present study, we investigate female urine-induced USVs, scent marking behavior, and open field activity in NS-Pten KO and wildtype (WT) adult male mice. Results showed that there was no difference in the quantity of vocalizations produced between groups, however, there were extensive alterations in the spectral properties of USVs. KO mice emitted vocalizations of a lower peak frequency, shorter duration, and higher peak amplitude compared to WT mice. KO animals also emitted a significantly different distribution of call-types relative to controls, displaying increased complex and short calls, but fewer upward, chevron, frequency steps, and composite calls. No significant differences between groups were observed for scent marking behavior and there was no difference between groups in the amount of time spent near the female urine. Overall, this study demonstrated that mTOR hyperactivity contributes to communication deficits in adult mice.
NS-Pten 敲除(KO)小鼠表现出雷帕霉素靶蛋白(mTOR)的过度活跃,是自闭症谱系障碍(ASD)的模型。ASD 在交流方面存在明显缺陷,可以通过研究其在小鼠中的对应物——超声波发声(USVs)来阐明。虽然已经发现 NS-Pten KO 幼鼠的 USVs 发生了改变,但尚无研究评估这种交流缺陷是否会持续到成年期。在本研究中,我们调查了 NS-Pten KO 和野生型(WT)成年雄性小鼠的尿液诱导的 USVs、气味标记行为和旷场活动。结果表明,两组之间产生的发声量没有差异,但 USVs 的光谱特性发生了广泛改变。与 WT 小鼠相比,KO 小鼠发出的声音峰值频率更低、持续时间更短、峰值幅度更高。与对照组相比,KO 动物还发出了明显不同分布的叫声类型,表现出更多的复杂叫声和短叫声,但向上叫声、V 字形叫声、频率阶跃叫声和复合叫声较少。在气味标记行为方面,两组之间没有观察到显著差异,在靠近雌性尿液的时间方面,两组之间也没有差异。总的来说,这项研究表明,mTOR 过度活跃导致成年小鼠的交流缺陷。