BACKGROUND 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. OBJECTIVE /Hypothesis: The aim of this study was to investigate the ability of VNS paired with tones to restore auditory processing in Mecp2 transgenic rats. METHODS 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. RESULTS 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. CONCLUSION These results demonstrate that VNS-sound pairing may represent a strategy to enhance auditory function in individuals with Rett syndrome.

中文翻译：

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迷走神经刺激与音调配对在雷特综合征大鼠模型中恢复听觉处理

背景 Rett 综合征是一种罕见的神经系统疾病，与 X 连锁基因 MECP2 的突变有关。这种疾病主要影响女性，她们通常具有看似正常的早期发育，随后获得的技能退化。啮齿动物 Mecp2 模型表现出在患有雷特综合征的个体中观察到的许多经典神经异常和行为缺陷。与 Rett 综合征个体相似，杂合 Mecp2 大鼠的听觉辨别能力和听觉皮层反应均受损。可以增强听觉网络可塑性和改善听觉处理的疗法的开发有可能影响 Rett 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，可以在听觉网络中驱动强大的神经可塑性，并增强听觉治疗的益处。目的/假设：本研究的目的是研究 VNS 与音调配对恢复 Mecp2 转基因大鼠听觉处理的能力。方法 本研究使用了 17 只雌性杂合 Mecp2 大鼠和 8 只雌性野生型 (WT) 同窝仔鼠。大鼠每天暴露于与 VNS 配对的多种音调频率 300 次，持续 20 天。然后在 VNS 音调配对治疗或无治疗后检查听觉皮层反应。结果 我们的结果表明，与 WT 对照相比，Mecp2 突变改变了听觉皮层对声音的反应。与未治疗的 Mecp2 大鼠相比，Mecp2 大鼠的 VNS 音调配对提高了对音调和语音的皮质反应强度。此外，VNS 音调配对增加了神经反应中包含的信息，可用于区分不同的辅音。结论这些结果表明，VNS-声音配对可能代表了一种增强雷特综合征患者听觉功能的策略。