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Auteur M. E. MODI |
Documents disponibles écrits par cet auteur (2)
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Replicable in vivo physiological and behavioral phenotypes of the Shank3B null mutant mouse model of autism / S. C. DHAMNE in Molecular Autism, 8 (2017)
[article]
Titre : Replicable in vivo physiological and behavioral phenotypes of the Shank3B null mutant mouse model of autism Type de document : Texte imprimé et/ou numérique Auteurs : S. C. DHAMNE, Auteur ; J. L. SILVERMAN, Auteur ; C. E. SUPER, Auteur ; S. H. T. LAMMERS, Auteur ; M. Q. HAMEED, Auteur ; M. E. MODI, Auteur ; N. A. COPPING, Auteur ; M. C. PRIDE, Auteur ; D. G. SMITH, Auteur ; A. ROTENBERG, Auteur ; J. N. CRAWLEY, Auteur ; M. SAHIN, Auteur Article en page(s) : 26p. Langues : Anglais (eng) Mots-clés : Anxiety Autism Gamma oscillations Pentylenetetrazol Repetitive behavior Shank3B Social behavior Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a clinically and biologically heterogeneous condition characterized by social, repetitive, and sensory behavioral abnormalities. No treatments are approved for the core diagnostic symptoms of ASD. To enable the earliest stages of therapeutic discovery and development for ASD, robust and reproducible behavioral phenotypes and biological markers are essential to establish in preclinical animal models. The goal of this study was to identify electroencephalographic (EEG) and behavioral phenotypes that are replicable between independent cohorts in a mouse model of ASD. The larger goal of our strategy is to empower the preclinical biomedical ASD research field by generating robust and reproducible behavioral and physiological phenotypes in animal models of ASD, for the characterization of mechanistic underpinnings of ASD-relevant phenotypes, and to ensure reliability for the discovery of novel therapeutics. Genetic disruption of the SHANK3 gene, a scaffolding protein involved in the stability of the postsynaptic density in excitatory synapses, is thought to be responsible for a relatively large number of cases of ASD. Therefore, we have thoroughly characterized the robustness of ASD-relevant behavioral phenotypes in two cohorts, and for the first time quantified translational EEG activity in Shank3B null mutant mice. METHODS: In vivo physiology and behavioral assays were conducted in two independently bred and tested full cohorts of Shank3B null mutant (Shank3B KO) and wildtype littermate control (WT) mice. EEG was recorded via wireless implanted telemeters for 7 days of baseline followed by 20 min of recording following pentylenetetrazol (PTZ) challenge. Behaviors relevant to the diagnostic and associated symptoms of ASD were tested on a battery of established behavioral tests. Assays were designed to reproduce and expand on the original behavioral characterization of Shank3B KO mice. Two or more corroborative tests were conducted within each behavioral domain, including social, repetitive, cognitive, anxiety-related, sensory, and motor categories of assays. RESULTS: Relative to WT mice, Shank3B KO mice displayed a dramatic resistance to PTZ seizure induction and an enhancement of gamma band oscillatory EEG activity indicative of enhanced inhibitory tone. These findings replicated in two separate cohorts. Behaviorally, Shank3B KO mice exhibited repetitive grooming, deficits in aspects of reciprocal social interactions and vocalizations, and reduced open field activity, as well as variable deficits in sensory responses, anxiety-related behaviors, learning and memory. CONCLUSIONS: Robust animal models and quantitative, replicable biomarkers of neural dysfunction are needed to decrease risk and enable successful drug discovery and development for ASD and other neurodevelopmental disorders. Complementary to the replicated behavioral phenotypes of the Shank3B mutant mouse is the new identification of a robust, translational in vivo neurophysiological phenotype. Our findings provide strong evidence for robustness and replicability of key translational phenotypes in Shank3B mutant mice and support the usefulness of this mouse model of ASD for therapeutic discovery. En ligne : http://dx.doi.org/10.1186/s13229-017-0142-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330
in Molecular Autism > 8 (2017) . - 26p.[article] Replicable in vivo physiological and behavioral phenotypes of the Shank3B null mutant mouse model of autism [Texte imprimé et/ou numérique] / S. C. DHAMNE, Auteur ; J. L. SILVERMAN, Auteur ; C. E. SUPER, Auteur ; S. H. T. LAMMERS, Auteur ; M. Q. HAMEED, Auteur ; M. E. MODI, Auteur ; N. A. COPPING, Auteur ; M. C. PRIDE, Auteur ; D. G. SMITH, Auteur ; A. ROTENBERG, Auteur ; J. N. CRAWLEY, Auteur ; M. SAHIN, Auteur . - 26p.
Langues : Anglais (eng)
in Molecular Autism > 8 (2017) . - 26p.
Mots-clés : Anxiety Autism Gamma oscillations Pentylenetetrazol Repetitive behavior Shank3B Social behavior Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a clinically and biologically heterogeneous condition characterized by social, repetitive, and sensory behavioral abnormalities. No treatments are approved for the core diagnostic symptoms of ASD. To enable the earliest stages of therapeutic discovery and development for ASD, robust and reproducible behavioral phenotypes and biological markers are essential to establish in preclinical animal models. The goal of this study was to identify electroencephalographic (EEG) and behavioral phenotypes that are replicable between independent cohorts in a mouse model of ASD. The larger goal of our strategy is to empower the preclinical biomedical ASD research field by generating robust and reproducible behavioral and physiological phenotypes in animal models of ASD, for the characterization of mechanistic underpinnings of ASD-relevant phenotypes, and to ensure reliability for the discovery of novel therapeutics. Genetic disruption of the SHANK3 gene, a scaffolding protein involved in the stability of the postsynaptic density in excitatory synapses, is thought to be responsible for a relatively large number of cases of ASD. Therefore, we have thoroughly characterized the robustness of ASD-relevant behavioral phenotypes in two cohorts, and for the first time quantified translational EEG activity in Shank3B null mutant mice. METHODS: In vivo physiology and behavioral assays were conducted in two independently bred and tested full cohorts of Shank3B null mutant (Shank3B KO) and wildtype littermate control (WT) mice. EEG was recorded via wireless implanted telemeters for 7 days of baseline followed by 20 min of recording following pentylenetetrazol (PTZ) challenge. Behaviors relevant to the diagnostic and associated symptoms of ASD were tested on a battery of established behavioral tests. Assays were designed to reproduce and expand on the original behavioral characterization of Shank3B KO mice. Two or more corroborative tests were conducted within each behavioral domain, including social, repetitive, cognitive, anxiety-related, sensory, and motor categories of assays. RESULTS: Relative to WT mice, Shank3B KO mice displayed a dramatic resistance to PTZ seizure induction and an enhancement of gamma band oscillatory EEG activity indicative of enhanced inhibitory tone. These findings replicated in two separate cohorts. Behaviorally, Shank3B KO mice exhibited repetitive grooming, deficits in aspects of reciprocal social interactions and vocalizations, and reduced open field activity, as well as variable deficits in sensory responses, anxiety-related behaviors, learning and memory. CONCLUSIONS: Robust animal models and quantitative, replicable biomarkers of neural dysfunction are needed to decrease risk and enable successful drug discovery and development for ASD and other neurodevelopmental disorders. Complementary to the replicated behavioral phenotypes of the Shank3B mutant mouse is the new identification of a robust, translational in vivo neurophysiological phenotype. Our findings provide strong evidence for robustness and replicability of key translational phenotypes in Shank3B mutant mice and support the usefulness of this mouse model of ASD for therapeutic discovery. En ligne : http://dx.doi.org/10.1186/s13229-017-0142-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome / M. G. MARISCAL in Molecular Autism, 12 (2021)
[article]
Titre : Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome Type de document : Texte imprimé et/ou numérique Auteurs : M. G. MARISCAL, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Joseph D. BUXBAUM, Auteur ; L. E. ETHRIDGE, Auteur ; R. FILIP-DHIMA, Auteur ; J. H. FOSS-FEIG, Auteur ; A. KOLEVZON, Auteur ; M. E. MODI, Auteur ; M. W. MOSCONI, Auteur ; C. A. NELSON, Auteur ; C. M. POWELL, Auteur ; P. M. SIPER, Auteur ; L. SOORYA, Auteur ; A. THALIATH, Auteur ; A. THURM, Auteur ; B. ZHANG, Auteur ; M. SAHIN, Auteur ; A. R. LEVIN, Auteur Article en page(s) : 29 p. Langues : Anglais (eng) Mots-clés : Cross-frequency coupling Eeg Phase bias Phelan-McDermid syndrome Power Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid Syndrome (PMS) is a rare condition caused by deletion or mutation of the SHANK3 gene. Individuals with PMS frequently present with intellectual disability, autism spectrum disorder, and other neurodevelopmental challenges. Electroencephalography (EEG) can provide a window into network-level function in PMS. METHODS: Here, we analyze EEG data collected across multiple sites in individuals with PMS (n?=?26) and typically developing individuals (n?=?15). We quantify oscillatory power, alpha-gamma phase-amplitude coupling strength, and phase bias, a measure of the phase of cross frequency coupling thought to reflect the balance of feedforward (bottom-up) and feedback (top-down) activity. RESULTS: We find individuals with PMS display increased alpha-gamma phase bias (U?=?3.841, p?0.0005), predominantly over posterior electrodes. Most individuals with PMS demonstrate positive overall phase bias while most typically developing individuals demonstrate negative overall phase bias. Among individuals with PMS, strength of alpha-gamma phase-amplitude coupling was associated with Sameness, Ritualistic, and Compulsive behaviors as measured by the Repetitive Behavior Scales-Revised (Beta?=?0.545, p?=?0.011). CONCLUSIONS: Increased phase bias suggests potential circuit-level mechanisms underlying phenotype in PMS, offering opportunities for back-translation of findings into animal models and targeting in clinical trials. En ligne : http://dx.doi.org/10.1186/s13229-020-00411-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 12 (2021) . - 29 p.[article] Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome [Texte imprimé et/ou numérique] / M. G. MARISCAL, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Joseph D. BUXBAUM, Auteur ; L. E. ETHRIDGE, Auteur ; R. FILIP-DHIMA, Auteur ; J. H. FOSS-FEIG, Auteur ; A. KOLEVZON, Auteur ; M. E. MODI, Auteur ; M. W. MOSCONI, Auteur ; C. A. NELSON, Auteur ; C. M. POWELL, Auteur ; P. M. SIPER, Auteur ; L. SOORYA, Auteur ; A. THALIATH, Auteur ; A. THURM, Auteur ; B. ZHANG, Auteur ; M. SAHIN, Auteur ; A. R. LEVIN, Auteur . - 29 p.
Langues : Anglais (eng)
in Molecular Autism > 12 (2021) . - 29 p.
Mots-clés : Cross-frequency coupling Eeg Phase bias Phelan-McDermid syndrome Power Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid Syndrome (PMS) is a rare condition caused by deletion or mutation of the SHANK3 gene. Individuals with PMS frequently present with intellectual disability, autism spectrum disorder, and other neurodevelopmental challenges. Electroencephalography (EEG) can provide a window into network-level function in PMS. METHODS: Here, we analyze EEG data collected across multiple sites in individuals with PMS (n?=?26) and typically developing individuals (n?=?15). We quantify oscillatory power, alpha-gamma phase-amplitude coupling strength, and phase bias, a measure of the phase of cross frequency coupling thought to reflect the balance of feedforward (bottom-up) and feedback (top-down) activity. RESULTS: We find individuals with PMS display increased alpha-gamma phase bias (U?=?3.841, p?0.0005), predominantly over posterior electrodes. Most individuals with PMS demonstrate positive overall phase bias while most typically developing individuals demonstrate negative overall phase bias. Among individuals with PMS, strength of alpha-gamma phase-amplitude coupling was associated with Sameness, Ritualistic, and Compulsive behaviors as measured by the Repetitive Behavior Scales-Revised (Beta?=?0.545, p?=?0.011). CONCLUSIONS: Increased phase bias suggests potential circuit-level mechanisms underlying phenotype in PMS, offering opportunities for back-translation of findings into animal models and targeting in clinical trials. En ligne : http://dx.doi.org/10.1186/s13229-020-00411-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459