Closing the species gap: Translational approaches to studying sensory processing differences relevant for autism spectrum disorder / Kaela E. SCOTT in Autism Research, 14-7 (July 2021)  

Public ISBD [article]  inAutism Research > 14-7 (July 2021) . - p.1322-1331 Titre : Closing the species gap: Translational approaches to studying sensory processing differences relevant for autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Kaela E. SCOTT, Auteur ; S. E. SCHULZ, Auteur ; D. MOEHRLE, Auteur ; Brian L. ALLMAN, Auteur ; Janis ORAM CARDY, Auteur ; R. A. STEVENSON, Auteur ; S. SCHMID, Auteur Article en page(s) : p.1322-1331 Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder  Cognition  Evoked Potentials  Humans  Mice  Perception  Sensation  auditory processing  experimental design  framework  sensory phenotypes  species translation Index. décimale : PER Périodiques Résumé : The study of sensory phenotypes has great potential for increasing research translation between species, a necessity to decipher the neural mechanisms that contribute to higher-order differences in neurological conditions such as autism spectrum disorder (ASD). Over the past decade, despite separate advances in our understanding of the structural and functional differences within the brain of autistic and non-autistic individuals and in rodent models for ASD, researchers have had difficulty translating the findings in murine species to humans, mostly due to incompatibility in experimental methodologies used to screen for ASD phenotypes. Focusing on sensory phenotypes offers an avenue to close the species gap because sensory pathways are highly conserved across species and are affected by the same risk-factors as the higher-order brain areas mostly responsible for the diagnostic criteria for ASD. By first reviewing how sensory processing has been studied to date, we direct our focus to electrophysiological and behavioral techniques that can be used to study sensory phenotypes consistently across species. Using auditory sensory phenotypes as a template, we seek to improve the accessibility of translational methods by providing a framework for collecting cohesive data in both rodents and humans. Specifically, evoked-potentials, acoustic startle paradigms, and psychophysical detection/discrimination paradigms can be created and implemented in a coordinated and systematic fashion across species. Through careful protocol design and collaboration, sensory processing phenotypes can be harnessed to bridge the gap that exists between preclinical animal studies and human testing, so that mutually held questions in autism research can be answered. LAY SUMMARY: It has always been difficult to relate results from animal research to humans. We try to close this gap by studying changes in sensory processing using careful protocol design and collaboration between clinicians and researchers. Sensory pathways are comparable between animals and humans, and are affected in the same way as the rest of the brain in ASD. Using changes in hearing as a template, we point the field in an innovative direction by providing a framework for collecting cohesive data in rodents and humans. En ligne : http://dx.doi.org/10.1002/aur.2533 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449 [article] Closing the species gap: Translational approaches to studying sensory processing differences relevant for autism spectrum disorder [Texte imprimé et/ou numérique] / Kaela E. SCOTT, Auteur ; S. E. SCHULZ, Auteur ; D. MOEHRLE, Auteur ; Brian L. ALLMAN, Auteur ; Janis ORAM CARDY, Auteur ; R. A. STEVENSON, Auteur ; S. SCHMID, Auteur . - p.1322-1331. Langues : Anglais (eng) in Autism Research > 14-7 (July 2021) . - p.1322-1331 Mots-clés : Animals  Autism Spectrum Disorder  Cognition  Evoked Potentials  Humans  Mice  Perception  Sensation  auditory processing  experimental design  framework  sensory phenotypes  species translation Index. décimale : PER Périodiques Résumé : The study of sensory phenotypes has great potential for increasing research translation between species, a necessity to decipher the neural mechanisms that contribute to higher-order differences in neurological conditions such as autism spectrum disorder (ASD). Over the past decade, despite separate advances in our understanding of the structural and functional differences within the brain of autistic and non-autistic individuals and in rodent models for ASD, researchers have had difficulty translating the findings in murine species to humans, mostly due to incompatibility in experimental methodologies used to screen for ASD phenotypes. Focusing on sensory phenotypes offers an avenue to close the species gap because sensory pathways are highly conserved across species and are affected by the same risk-factors as the higher-order brain areas mostly responsible for the diagnostic criteria for ASD. By first reviewing how sensory processing has been studied to date, we direct our focus to electrophysiological and behavioral techniques that can be used to study sensory phenotypes consistently across species. Using auditory sensory phenotypes as a template, we seek to improve the accessibility of translational methods by providing a framework for collecting cohesive data in both rodents and humans. Specifically, evoked-potentials, acoustic startle paradigms, and psychophysical detection/discrimination paradigms can be created and implemented in a coordinated and systematic fashion across species. Through careful protocol design and collaboration, sensory processing phenotypes can be harnessed to bridge the gap that exists between preclinical animal studies and human testing, so that mutually held questions in autism research can be answered. LAY SUMMARY: It has always been difficult to relate results from animal research to humans. We try to close this gap by studying changes in sensory processing using careful protocol design and collaboration between clinicians and researchers. Sensory pathways are comparable between animals and humans, and are affected in the same way as the rest of the brain in ASD. Using changes in hearing as a template, we point the field in an innovative direction by providing a framework for collecting cohesive data in rodents and humans. En ligne : http://dx.doi.org/10.1002/aur.2533 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449

Loss of Cntnap2 in the Rat Causes Autism-Related Alterations in Social Interactions, Stereotypic Behavior, and Sensory Processing / Kaela E. SCOTT in Autism Research, 13-10 (October 2020)  

Public ISBD [article]  inAutism Research > 13-10 (October 2020) . - p.1698-1717 Titre : Loss of Cntnap2 in the Rat Causes Autism-Related Alterations in Social Interactions, Stereotypic Behavior, and Sensory Processing Type de document : Texte imprimé et/ou numérique Auteurs : Kaela E. SCOTT, Auteur ; Karnig KAZAZIAN, Auteur ; Rajkamalpreet S. MANN, Auteur ; Dorit MÖHRLE, Auteur ; Ashley L. SCHORMANS, Auteur ; Susanne SCHMID, Auteur ; Brian L. ALLMAN, Auteur Article en page(s) : p.1698-1717 Langues : Anglais (eng) Mots-clés : Cntnap2  animal model  autism spectrum disorder  behavior  sensory  social  startle Index. décimale : PER Périodiques Résumé : 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. En ligne : http://dx.doi.org/10.1002/aur.2364 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=431 [article] Loss of Cntnap2 in the Rat Causes Autism-Related Alterations in Social Interactions, Stereotypic Behavior, and Sensory Processing [Texte imprimé et/ou numérique] / Kaela E. SCOTT, Auteur ; Karnig KAZAZIAN, Auteur ; Rajkamalpreet S. MANN, Auteur ; Dorit MÖHRLE, Auteur ; Ashley L. SCHORMANS, Auteur ; Susanne SCHMID, Auteur ; Brian L. ALLMAN, Auteur . - p.1698-1717. Langues : Anglais (eng) in Autism Research > 13-10 (October 2020) . - p.1698-1717 Mots-clés : Cntnap2  animal model  autism spectrum disorder  behavior  sensory  social  startle Index. décimale : PER Périodiques Résumé : 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. En ligne : http://dx.doi.org/10.1002/aur.2364 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=431

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