Deficits in skilled motor and auditory learning in a rat model of Rett syndrome
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(2020) 12:27
RESEARCH
Open Access
Deficits in skilled motor and auditory learning in a rat model of Rett syndrome Katherine S. Adcock1,2* , Abigail E. Blount2, Robert A. Morrison1,2, Amanda Alvarez-Dieppa1, Michael P. Kilgard1,2,3, Crystal T. Engineer1,2 and Seth A. Hays1,2,3
Abstract Background: 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. Methods: 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. Results: 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. Conclusions: 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. Keywords: Rett syndrome, MeCP2, Motor, Auditory, Learning
Background Rett syndrome is a rare neurodevelopmental disorder associated with a mutation in the X-linked gene MECP2. This disorder mostly affects females, who display normal early development followed by regression of already acquired skills [4]. Individuals with Rett syndrome exhibit a range of symptoms, including seizures, breathing abnormalities, motor impairments, changes in sensory responses, anxiety, and speech-language deficits [4, 14].
* Correspondence: [email protected] 1 School of Behavioral and Brain Sciences, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080-3021, USA 2 Texas Biomedical Device Center, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080-3021, USA Full list of author information is available at the end of the article
The development of interventional strategies to improve function in these domains is of clear clinical importance. To address this and provide a testbed for evaluation, transgenic mouse and rat models bearing mutations in the MECP2 gene have been developed [12, 13, 25, 31]. Some features of these models have been well characterized and provide substantial insight into the pathophysiology of Rett syndrome. However, testing complex behaviors in Mecp2 rodents is in its early stages. Initial work successfully modeled psychomotor regression simi
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