Pultorak Joshua D, Kelm-Nelson Cynthia A, Holt Lauren R, Blue Katherine V, Ciucci Michelle R, Johnson Aaron M
a Department of Zoology , University of Wisconsin-Madison , Madison , WI , USA.
b Department of Surgery, Division of Otolaryngology , University of Wisconsin-Madison , Madison , WI , USA.
Soc Neurosci. 2016;11(4):365-79. doi: 10.1080/17470919.2015.1086434. Epub 2015 Sep 14.
Many individuals with Parkinson disease (PD) have difficulty producing normal speech and voice, resulting in problems with interpersonal communication and reduced quality of life. Translational animal models of communicative dysfunction have been developed to assess disease pathology. However, it is unknown whether acoustic feature changes associated with vocal production deficits in these animal models lead to compromised communication. In rodents, male ultrasonic vocalizations (USVs) have a well-established role in functional inter-sexual communication. To test whether acoustic deficits in USVs observed in a PTEN-induced putative kinase 1 (PINK1) knockout (KO) PD rat model compromise communication, we presented recordings of male PINK1 KO USVs and normal wild-type (WT) USVs to female rat listeners. We measured approached behavior and immediate early gene expression (c-Fos) in brain regions implicated in auditory processing and sexual motivation. Our results suggest that females show reduced approach in response to PINK1 KO USVs compared with WT. Moreover, females exposed to PINK1 KO USVs had lower c-Fos immunolabeling in the nucleus accumbens, a region implicated in sexual motivation. These results are the first to demonstrate that vocalization deficits in a rat PD model result in compromised communication. Thus, the PINK1 KO PD model may be valuable for assessing treatments aimed at restoring vocal communicative function.
许多帕金森病(PD)患者在产生正常语音和声音方面存在困难,导致人际沟通出现问题,生活质量下降。已开发出交流功能障碍的转化动物模型来评估疾病病理。然而,尚不清楚这些动物模型中与发声缺陷相关的声学特征变化是否会导致沟通受损。在啮齿动物中,雄性超声波发声(USV)在功能性两性间交流中具有既定作用。为了测试在PTEN诱导的假定激酶1(PINK1)基因敲除(KO)PD大鼠模型中观察到的USV声学缺陷是否会损害交流,我们向雌性大鼠听众播放了雄性PINK1 KO USV和正常野生型(WT)USV的录音。我们测量了与听觉处理和性动机相关的脑区中的接近行为和即刻早期基因表达(c-Fos)。我们的结果表明,与WT相比,雌性对PINK1 KO USV的反应中接近行为减少。此外,暴露于PINK1 KO USV的雌性大鼠伏隔核中的c-Fos免疫标记较低,伏隔核是一个与性动机相关的区域。这些结果首次证明大鼠PD模型中的发声缺陷会导致沟通受损。因此,PINK1 KO PD模型可能对评估旨在恢复语音交流功能的治疗方法有价值。