scholarly journals Deficits in Skilled Motor and Auditory Learning in a Rat Model of Rett Syndrome

2020 ◽  
Author(s):  
Katherine S. Adcock ◽  
Abigail E. Blount ◽  
Robert A. Morrison ◽  
Amanda Alvarez-Dieppa ◽  
Michael P. Kilgard ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Discrimination Task ◽  
Neurodevelopmental Disorder ◽  
Motor Task ◽  
Speech Discrimination ◽  
Auditory Learning ◽  
Reaching Task ◽  
Developmental Regression ◽  
Learning Rates ◽  
And Performance

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.

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

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Katherine S. Adcock ◽  
Abigail E. Blount ◽  
Robert A. Morrison ◽  
Amanda Alvarez-Dieppa ◽  
Michael P. Kilgard ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Discrimination Task ◽  
Neurodevelopmental Disorder ◽  
Motor Task ◽  
Speech Discrimination ◽  
Auditory Learning ◽  
Reaching Task ◽  
Developmental Regression ◽  
Learning Rates ◽  
And Performance

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.

scholarly journals Deficits in Skilled Motor and Auditory Learning in a Rat Model of Rett Syndrome

2020 ◽  
Author(s):  
Katherine S. Adcock ◽  
Abigail E. Blount ◽  
Robert A. Morrison ◽  
Amanda Alvarez-Dieppa ◽  
Michael P. Kilgard ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Discrimination Task ◽  
Neurodevelopmental Disorder ◽  
Motor Task ◽  
Speech Discrimination ◽  
Auditory Learning ◽  
Reaching Task ◽  
Developmental Regression ◽  
Learning Rates ◽  
And Performance

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.

scholarly journals Deficits in Skilled Motor and Auditory Learning in a Rat Model of Rett Syndrome

2020 ◽  
Author(s):  
Katherine S. Adcock ◽  
Abigail E. Blount ◽  
Robert A. Morrison ◽  
Amanda Alvarez-Dieppa ◽  
Michael P. Kilgard ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Discrimination Task ◽  
Neurodevelopmental Disorder ◽  
Motor Task ◽  
Speech Discrimination ◽  
Auditory Learning ◽  
Reaching Task ◽  
Developmental Regression ◽  
Learning Rates ◽  
And Performance

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.

scholarly journals MeCP2: The Genetic Driver of Rett Syndrome Epigenetics

2021 ◽  
Vol 12 ◽  
Author(s):  
Katrina V. Good ◽  
John B. Vincent ◽  
Juan Ausió
Keyword(s):  
Rett Syndrome ◽  
Neuronal Development ◽  
Neurodevelopmental Disorder ◽  
Epigenetic Mark ◽  
Initial Development ◽  
Genetic Ablation ◽  
Developmental Regression ◽  
The Stability ◽  
The Brain

Mutations in methyl CpG binding protein 2 (MeCP2) are the major cause of Rett syndrome (RTT), a rare neurodevelopmental disorder with a notable period of developmental regression following apparently normal initial development. Such MeCP2 alterations often result in changes to DNA binding and chromatin clustering ability, and in the stability of this protein. Among other functions, MeCP2 binds to methylated genomic DNA, which represents an important epigenetic mark with broad physiological implications, including neuronal development. In this review, we will summarize the genetic foundations behind RTT, and the variable degrees of protein stability exhibited by MeCP2 and its mutated versions. Also, past and emerging relationships that MeCP2 has with mRNA splicing, miRNA processing, and other non-coding RNAs (ncRNA) will be explored, and we suggest that these molecules could be missing links in understanding the epigenetic consequences incurred from genetic ablation of this important chromatin modifier. Importantly, although MeCP2 is highly expressed in the brain, where it has been most extensively studied, the role of this protein and its alterations in other tissues cannot be ignored and will also be discussed. Finally, the additional complexity to RTT pathology introduced by structural and functional implications of the two MeCP2 isoforms (MeCP2-E1 and MeCP2-E2) will be described. Epigenetic therapeutics are gaining clinical popularity, yet treatment for Rett syndrome is more complicated than would be anticipated for a purely epigenetic disorder, which should be taken into account in future clinical contexts.

Videofluororadiographic Descriptors of Swallowing Physiology in Typical Rett Syndrome: Post-Regression Stabilization During Early Childhood

2012 ◽  
Vol 21 (4) ◽  
pp. 121-125 ◽  
Author(s):  
Suzanne S. Abraham
Keyword(s):  
Early Childhood ◽  
Gene Mutation ◽  
Rett Syndrome ◽  
Chromosomal Abnormality ◽  
Clinical Phenotype ◽  
Neurodevelopmental Disorder ◽  
Chromosome X ◽  
Developmental Regression ◽  
Core Features

Typical or classic Rett syndrome (RTT) is the only pervasive neurodevelopmental disorder with a known chromosomal abnormality. Despite differences in clinical phenotype of girls with RTT who share the same gene mutation on chromosome X, there is commonality in the stages and core features of this profoundly disabling disorder, including the deterioration of acquired vocal behaviors and meaningful speech during the regression stage. The purpose of this article is to ascertain any commonality in the swallowing neurophysiology of a select sample of girls with typical RTT who were under the age of 5 years and had undergone the devastating effects of developmental regression.

scholarly journals Rett Syndrome: A Case Report

1970 ◽  
Vol 28 (1) ◽  
pp. 20-22
Author(s):  
MR Pathak ◽  
A Neopane
Keyword(s):  
Rett Syndrome ◽  
Speech Therapy ◽  
Neurodevelopmental Disorder ◽  
Mecp2 Gene ◽  
Dominant Inheritance ◽  
Pharmacological Agents ◽  
Developmental Regression ◽  
History Of ◽  
Social Interaction Skills ◽  
Key Words Rett Syndrome

Rett Syndrome (RS) is a neurodevelopmental disorder in which girls are predominantly affected, transmitted as an X linked dominant inheritance and caused by mutation in MECP2 gene. The basic presentation in RS is regression of previously acquired developmental milestones, lack of social interaction skills and acquired microcephaly after a certain age, which starts in early months of infancy. It is frequently misdiagnosed as autism, cerebral palsy or nonspecific developmental delay and is relatively frequent cause of delayed development in girls. Diagnosis is mainly clinical after excluding the neurodegenerative and other causes of delayed milestones. The chromosomal analysis, confirmatory tool for diagnosis is available in limited centers. The treatment is mainly speech therapy and counseling though few pharmacological agents have been tried with little response. A ten years age girl presented with the history of seizures, regression of speech and delayed motor milestones in our out patient clinic which was subsequently diagnosed as Rett Syndrome. Key Words: Rett syndrome, Developmental Regression, X Linked Dominant.    DOI = 10.3126/jnps.v28i1.1402   J. Nepal Paediatr. Soc. Vol.28(1) p.20-22

scholarly journals Distinct contributions of three GABAergic interneuron populations to a mouse model of Rett Syndrome

2017 ◽  
Author(s):  
James M. Mossner ◽  
Renata Batista-Brito ◽  
Rima Pant ◽  
Jessica A. Cardin
Keyword(s):  
Rett Syndrome ◽  
Neurodevelopmental Disorder ◽  
Cell Types ◽  
Gabaergic Interneuron ◽  
Loss Of Function ◽  
Behavioral Phenotypes ◽  
Motor Behaviors ◽  
Marble Burying ◽  
And Performance ◽  
The Brain

AbstractBackgroundRett Syndrome is a devastating neurodevelopmental disorder resulting from mutations in the gene MeCP2. MeCP2 is a transcriptional regulator active in many cell types throughout the brain. However, mutations of MeCP2 restricted to GABAergic cell types largely replicate the behavioral phenotypes associated with mouse models of Rett Syndrome, suggesting a key role for inhibitory interneurons in the pathophysiology underlying this disorder.MethodsWe generated conditional deletions of MeCP2 from each of three major classes of GABAergic interneurons, the parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptide (VIP)-expressing cells, along with a pan-interneuron deletion from all three GABAergic populations. We examined seizure incidence, mortality, and performance on several key behavioral assays.ResultsWe find that each interneuron class makes a contribution to the seizure phenotype associated with Rett Syndrome. PV, SOM, and VIP interneurons made partially overlapping contributions to deficits in motor behaviors. We find little evidence for elevated anxiety associated with any of the conditional deletions. However, MeCP2 deletion from VIP interneurons causes a unique deficit in marble burying. Furthermore, VIP interneurons make a distinct contribution to deficits in social behavior.ConclusionsWe find an unanticipated contribution of VIP interneuron dysfunction to the MeCP2 loss-of-function model of Rett Syndrome. Together, our findings suggest a complex interaction between GABAergic dysfunction and behavioral phenotypes in this neurodevelopmental disorder.

Stimulus Ratio Effects on Speech Discrimination by Children and Adults

1991 ◽  
Vol 34 (3) ◽  
pp. 671-678 ◽  
Author(s):  
Joan E. Sussman
Keyword(s):  
Discrimination Task ◽  
Response Pattern ◽  
Response Patterns ◽  
Speech Discrimination ◽  
Adult Group ◽  
Discrimination Accuracy ◽  
Formant Frequency ◽  
Response Strategies ◽  
Place Of Articulation ◽  
Adults And Children

This investigation examined the response strategies and discrimination accuracy of adults and children aged 5–10 as the ratio of same to different trials was varied across three conditions of a “change/no-change” discrimination task. The conditions varied as follows: (a) a ratio of one-third same to two-thirds different trials (33% same), (b) an equal ratio of same to different trials (50% same), and (c) a ratio of two-thirds same to one-third different trials (67% same). Stimuli were synthetic consonant-vowel syllables that changed along a place of articulation dimension by formant frequency transition. Results showed that all subjects changed their response strategies depending on the ratio of same-to-different trials. The most lax response pattern was observed for the 50% same condition, and the most conservative pattern was observed for the 67% same condition. Adult response patterns were most conservative across condition. Differences in discrimination accuracy as measured by P(C) were found, with the largest difference in the 5- to 6-year-old group and the smallest change in the adult group. These findings suggest that children’s response strategies, like those of adults, can be manipulated by changing the ratio of same-to-different trials. Furthermore, interpretation of sensitivity measures must be referenced to task variables such as the ratio of same-to-different trials.

scholarly journals An Agent-Specific Stochastic Model of Generalized Reaching Task Difficulty

2021 ◽  
Vol 11 (10) ◽  
pp. 4330
Author(s):  
Andrea Lucchese ◽  
Salvatore Digiesi ◽  
Kübra Akbaş ◽  
Carlotta Mummolo
Keyword(s):  
Stochastic Model ◽  
Task Difficulty ◽  
Motor Task ◽  
Younger Adults ◽  
Reaching Task ◽  
Index Of Difficulty ◽  
Young Subjects ◽  
Aged Subjects ◽  
Spatial Trajectories ◽  
Repetitive Motor

The ability of an agent to accomplish a trajectory during a certain motor task depends on the fit between external (environment) and internal (agent) constraints, also known as affordance. A model of difficulty for a generalized reaching motor task is proposed as an affordance-related measure, as perceived by a specific agent for a given environment and task. By extending the information-based Index of Difficulty of a trajectory, a stochastic model of difficulty is formulated based on the observed variability of spatial trajectories executed by a given agent during a repetitive motor task. The model is tested on an experimental walking dataset available in the literature, where the repetitive stride movement of differently aged subjects (14 “old” subjects aged 50–73; 20 “young” subjects aged 21–37) at multiple speed conditions (comfortable, ~30% faster, ~30% slower) is analyzed. Reduced trajectory variability in older as compared to younger adults results in a higher Index of Difficulty (slower: +24%, p < 0.0125; faster: +38%, p < 0.002) which is interpreted in this context as reduced affordance. The model overcomes the limits of existing difficulty measures by capturing the stochastic dependency of task difficulty on a subject’s age and average speed. This model provides a benchmarking tool for motor performance in biomechanics and ergonomics applications.

Trait and State Anxiety before and after Competitive Performance

1995 ◽  
Vol 81 (3_suppl) ◽  
pp. 1059-1074 ◽  
Author(s):  
Hallgeir Halvari ◽  
Torgrim Gjesme
Keyword(s):  
State Anxiety ◽  
Motor Task ◽  
Muscular Activity ◽  
Critical Factor ◽  
Physical Strength ◽  
Performance Errors ◽  
Before And After ◽  
Trait And State Anxiety ◽  
Direction Of Movement ◽  
And Performance

33 subjects were tested on competitive trait and state anxiety immediately before and after a competitive motor task of short duration (average performance time of 25 seconds). It required precise coordination of correct muscular activity, timing as well as speed, and physical strength that included explosive shifts in direction of movement. Two types of performance measures were employed, (a) number of errors during the performance and (b) the time it took to complete the motor task. Analysis showed a positive relation between trait anxiety and performance errors when a linear model was applied; however, when a curvilinear model was used, a strong significant U-relationship between errors and precompetition state anxiety emerged. Further, a strong positive linear relation between poststate anxiety and number of performance errors was observed. The results indicate that making errors in performance situations is a critical factor in producing postcompetition state anxiety.

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