The University of Texas at Dallas, Texas Biomedical Device Center, 800 West Campbell Road BSB11, Richardson, TX, 75080, USA; The University of Texas at Dallas, School of Behavioral and Brain Sciences, 800 West Campbell Road BSB11, Richardson, TX, 75080, USA.
The University of Texas at Dallas, Texas Biomedical Device Center, 800 West Campbell Road BSB11, Richardson, TX, 75080, USA; The University of Texas at Dallas, Erik Jonsson School of Engineering and Computer Science, 800 West Campbell Road BSB11, Richardson, TX, 75080, USA.
Brain Stimul. 2020 Nov-Dec;13(6):1494-1503. doi: 10.1016/j.brs.2020.08.006. Epub 2020 Aug 12.
Rett syndrome is a rare neurological disorder associated with a mutation in the X-linked gene MECP2. This disorder mainly affects females, who typically have seemingly normal early development followed by a regression of acquired skills. The rodent Mecp2 model exhibits many of the classic neural abnormalities and behavioral deficits observed in individuals with Rett syndrome. Similar to individuals with Rett syndrome, both auditory discrimination ability and auditory cortical responses are impaired in heterozygous Mecp2 rats. The development of therapies that can enhance plasticity in auditory networks and improve auditory processing has the potential to impact the lives of individuals with Rett syndrome. Evidence suggests that precisely timed vagus nerve stimulation (VNS) paired with sound presentation can drive robust neuroplasticity in auditory networks and enhance the benefits of auditory therapy.
The aim of this study was to investigate the ability of VNS paired with tones to restore auditory processing in Mecp2 transgenic rats.
Seventeen female heterozygous Mecp2 rats and 8 female wild-type (WT) littermates were used in this study. The rats were exposed to multiple tone frequencies paired with VNS 300 times per day for 20 days. Auditory cortex responses were then examined following VNS-tone pairing therapy or no therapy.
Our results indicate that Mecp2 mutation alters auditory cortex responses to sounds compared to WT controls. VNS-tone pairing in Mecp2 rats improves the cortical response strength to both tones and speech sounds compared to untreated Mecp2 rats. Additionally, VNS-tone pairing increased the information contained in the neural response that can be used to discriminate between different consonant sounds.
These results demonstrate that VNS-sound pairing may represent a strategy to enhance auditory function in individuals with Rett syndrome.
雷特综合征是一种罕见的神经发育障碍，与 X 连锁基因 MECP2 的突变有关。这种疾病主要影响女性，她们通常有看似正常的早期发育，随后出现获得性技能的退化。啮齿动物 Mecp2 模型表现出许多与雷特综合征患者相同的典型神经异常和行为缺陷。与雷特综合征患者相似，杂合子 Mecp2 大鼠的听觉辨别能力和听觉皮层反应都受到损害。开发能够增强听觉网络可塑性并改善听觉处理的治疗方法，有可能改变雷特综合征患者的生活。有证据表明，精确定时的迷走神经刺激 (VNS) 与声音呈现相结合，可以驱动听觉网络中的强大神经可塑性，并增强听觉治疗的益处。
本研究旨在探讨 VNS 与音调结合是否能恢复 Mecp2 转基因大鼠的听觉处理能力。
本研究使用了 17 只雌性杂合子 Mecp2 大鼠和 8 只雌性野生型 (WT) 同窝仔鼠。这些大鼠每天接受 300 次多种音调与 VNS 的配对刺激，持续 20 天。然后，在接受 VNS-音调配对治疗或不接受治疗后，检查听觉皮层的反应。
我们的结果表明，Mecp2 突变改变了听觉皮层对声音的反应，与 WT 对照组相比。与未经治疗的 Mecp2 大鼠相比，VNS-音调配对在 Mecp2 大鼠中改善了皮质对音调及语音的反应强度。此外，VNS-音调配对增加了可用于区分不同辅音的神经反应中的信息含量。
这些结果表明，VNS-声音配对可能是增强雷特综合征患者听觉功能的一种策略。
