Deficits in skilled motor and auditory learning in a rat model of Rett syndrome.
Deficits in skilled motor and auditory learning in a rat model of Rett syndrome.
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DOI：
10.1186/s11689-020-09330-5
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发表时间：
2020-09-28
影响因子：
4.9
通讯作者：
Hays SA
中科院分区：
文献类型：
--
作者：
Adcock KS;Blount AE;Morrison RA;Alvarez-Dieppa A;Kilgard MP;Engineer CT;Hays SA
Rett 综合征是一种 X 连锁神经发育障碍，由 MECP2 基因突变引起。患有雷特综合征的人在很小的时候就表现出发育退化，并出现一系列运动、听觉、认知和社交障碍。几项研究已成功模拟了 MECP2 基因突变的转基因小鼠和大鼠模型中功能障碍和雷特综合征样表型的某些方面。在这里，我们试图扩展这些发现并描述技能学习的特征，这是一种已知在雷特综合征中发生改变的更复杂的行为。我们评估了杂合雌性 Mecp2 大鼠在两项复杂任务中听觉和运动功能的获得和表现。动物被训练执行言语辨别任务或熟练的前肢伸展任务。我们的结果表明，与野生型（WT）同窝小鼠相比，Mecp2 大鼠在听觉辨别任务中表现出较慢的获取速度和较低的表现。同样，与 WT 相比，Mecp2 大鼠的学习率受损，并且在熟练的前肢运动任务中表现较差。总之，这些发现说明了与雷特综合征的临床表现一致的技能学习的新缺陷，并为开发改善这些复杂行为的治疗策略提供了框架。
Rett syndrome is an X-linked neurodevelopmental disorder caused by a mutation in the gene MECP2. Individuals with Rett syndrome display developmental regression at an early age, and develop a range of motor, auditory, cognitive, and social impairments. Several studies have successfully modeled some aspects of dysfunction and Rett syndrome-like phenotypes in transgenic mouse and rat models bearing mutations in the MECP2 gene. Here, we sought to extend these findings and characterize skilled learning, a more complex behavior known to be altered in Rett syndrome. We evaluated the acquisition and performance of auditory and motor function on two complex tasks in heterozygous female Mecp2 rats. Animals were trained to perform a speech discrimination task or a skilled forelimb reaching task. Our results reveal that Mecp2 rats display slower acquisition and reduced performance on an auditory discrimination task than wild-type (WT) littermates. Similarly, Mecp2 rats exhibit impaired learning rates and worse performance on a skilled forelimb motor task compared to WT. Together, these findings illustrate novel deficits in skilled learning consistent with clinical manifestation of Rett syndrome and provide a framework for development of therapeutic strategies to improve these complex behaviors.
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影响因子：
5.1
作者：
Gandaglia, Anna;Brivio, Elena;Landsberger, Nicoletta
通讯作者：
Landsberger, Nicoletta
影响因子：
2.7
作者：
Engineer, Crystal T.;Perez, Claudia A.;Kilgard, Michael P.
通讯作者：
Kilgard, Michael P.
影响因子：
3.5
作者：
Patterson, Kelsey C.;Hawkins, Virginia E.;Olsen, Michelle L.
通讯作者：
Olsen, Michelle L.
影响因子：
25
作者：
Engineer, Crystal T.;Perez, Claudia A.;Kilgard, Michael P.
通讯作者：
Kilgard, Michael P.
影响因子：
7.7
作者：
Morrison, Robert A.;Hulsey, Daniel R.;Hays, Seth A.
通讯作者：
Hays, Seth A.