Loss of Cntnap2 in the Rat Causes Autism-Related Alterations in Social Interactions, Stereotypic Behavior, and Sensory Processing
| Autor: | Ashley L. Schormans, Susanne Schmid, Kaela E. Scott, Rajkamalpreet S Mann, Karnig Kazazian, Dorit Möhrle, Brian L. Allman |
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| Rok vydání: | 2020 |
| Předmět: |
CNTNAP2
Reflex Startle Sensory processing medicine.medical_treatment media_common.quotation_subject Social Interaction Sensory system autism spectrum disorder Nerve Tissue Proteins sensory behavioral disciplines and activities startle 03 medical and health sciences 0302 clinical medicine Perception Intellectual disability mental disorders medicine Animals 0501 psychology and cognitive sciences Autistic Disorder Social Behavior Genetics (clinical) media_common behavior General Neuroscience animal model 05 social sciences Membrane Proteins social medicine.disease Social relation Rats Autism spectrum disorder Autism Neurology (clinical) Psychology Neuroscience 030217 neurology & neurosurgery 050104 developmental & child psychology |
| Zdroj: | Brain and Mind Institute Researchers' Publications |
| ISSN: | 1939-3806 |
| Popis: | Autism spectrum disorder (ASD) is characterized by social interaction and communication impairments, as well as restrictive/repetitive patterns of behavior, interests or activities, which can coexist with intellectual disability and altered sensory processing. To study the mechanisms underlying these core features of ASD, preclinical research has developed animal models with manipulations in ASD-linked genes, such as CNTNAP2. In order to fully interpret the findings from mechanistic studies, the extent to which these models display behaviors consistent with ASD must be determined. Toward that goal, we conducted an investigation of the consequences of a functional loss of Cntnap2 on ASD-related behaviors by comparing the performance of rats with a homozygous or heterozygous knockout of Cntnap2 to their wildtype littermates across a comprehensive test battery. Cntnap2-/- rats showed deficits in sociability and social novelty, and they displayed repetitive circling and hyperlocomotion. Moreover, Cntnap2-/- rats demonstrated exaggerated acoustic startle responses, increased avoidance to sounds of moderate intensity, and a lack of rapid audiovisual temporal recalibration; indicating changes in sensory processing at both the pre-attentive and perceptual levels. Notably, sensory behaviors requiring learned associations did not reveal genotypic differences, whereas tasks relying on automatic/implicit behaviors did. Ultimately, because these collective alterations in social, stereotypic, and sensory behaviors are phenotypically similar to those reported in individuals with ASD, our results establish the Cntnap2 knockout rat model as an effective platform to study not only the molecular and cellular mechanisms associated with ASD, but also the complex relationship between altered sensory processing and other core ASD-related behaviors. LAY SUMMARY: Autism spectrum disorder (ASD) is characterized by social interaction differences, and restrictive/repetitive patterns of behavior. We studied the behavioral alterations caused by the loss of an autism-linked gene, Cntnap2, in the rat to determine how mutations in this gene contribute to autism-related behaviors. We show the loss of Cntnap2 leads to changes in social, stereotypic, and sensory behaviors, indicating this rat model can be used to better understand the brain changes underlying ASD. Autism Res 2020, 13: 1698-1717. © 2020 International Society for Autism Research and Wiley Periodicals LLC. |
| Databáze: | OpenAIRE |
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