Deficits in skilled motor and auditory learning in a rat model of Rett syndrome

Katherine S Adcock,Seth A Hays,Crystal T Engineer,Abigail E Blount,Amanda Alvarez-Dieppa,Robert A Morrison,Michael P Kilgard

doi:10.1186/s11689-020-09330-5

Katherine S Adcock, Seth A Hays + Show 5 more

Open Access

https://doi.org/10.1186/s11689-020-09330-5

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Abstract

BackgroundRett 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.MethodsWe 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.ResultsOur 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.ConclusionsTogether, 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.

Highlights

Rett syndrome is an X-linked neurodevelopmental disorder caused by a mutation in the gene MECP2
Impaired performance corresponds to dysregulated neural function in auditory and motor networks in transgenic Methyl CpG binding protein 2 (Mecp2) models [9, 21]. These results provide a novel characterization of skilled learning in Mecp2 rats and develop a framework for future studies to evaluate the effect of potential interventions on complex behavioral tasks
These findings are consistent with previous studies and suggest that gross auditory processing is generally intact in Mecp2 rodents [9, 12, 20]

Summary

Introduction

Rett syndrome is an X-linked neurodevelopmental disorder caused by a mutation in the gene MECP2. 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]. 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.

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