Abnormal coherence and sleep composition in children with Angelman syndrome: a retrospective EEG study / Hanna DEN BAKKER in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 32p. Titre : Abnormal coherence and sleep composition in children with Angelman syndrome: a retrospective EEG study Type de document : texte imprimé Auteurs : Hanna DEN BAKKER, Auteur ; Michael S. SIDOROV, Auteur ; Zheng FAN, Auteur ; David J. LEE, Auteur ; Lynne M. BIRD, Auteur ; Catherine J. CHU, Auteur ; Benjamin D. PHILPOT, Auteur Article en page(s) : 32p. Langues : Anglais (eng) Mots-clés : Angelman Syndrome/physiopathology  Case-Control Studies  Child  Delta Rhythm  Female  Gamma Rhythm  Humans  Male  Sleep Stages  Angelman syndrome  Biomarker  Coherence  eeg  Spindles  UBE3A Index. décimale : PER Périodiques Résumé : Background: Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, speech and motor impairments, epilepsy, abnormal sleep, and phenotypic overlap with autism. Individuals with AS display characteristic EEG patterns including high-amplitude rhythmic delta waves. Here, we sought to quantitatively explore EEG architecture in AS beyond known spectral power phenotypes. We were motivated by studies of functional connectivity and sleep spindles in autism to study these EEG readouts in children with AS. Methods: We analyzed retrospective wake and sleep EEGs from children with AS (age 4-11) and age-matched neurotypical controls. We assessed long-range and short-range functional connectivity by measuring coherence across multiple frequencies during wake and sleep. We quantified sleep spindles using automated and manual approaches. Results: During wakefulness, children with AS showed enhanced long-range EEG coherence across a wide range of frequencies. During sleep, children with AS showed increased long-range EEG coherence specifically in the gamma band. EEGs from children with AS contained fewer sleep spindles, and these spindles were shorter in duration than their neurotypical counterparts. Conclusions: We demonstrate two quantitative readouts of dysregulated sleep composition in children with AS-gamma coherence and spindles-and describe how functional connectivity patterns may be disrupted during wakefulness. Quantitative EEG phenotypes have potential as biomarkers and readouts of target engagement for future clinical trials and provide clues into how neural circuits are dysregulated in children with AS. En ligne : https://dx.doi.org/10.1186/s13229-018-0214-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 [article] Abnormal coherence and sleep composition in children with Angelman syndrome: a retrospective EEG study [texte imprimé] / Hanna DEN BAKKER, Auteur ; Michael S. SIDOROV, Auteur ; Zheng FAN, Auteur ; David J. LEE, Auteur ; Lynne M. BIRD, Auteur ; Catherine J. CHU, Auteur ; Benjamin D. PHILPOT, Auteur . - 32p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 32p. Mots-clés : Angelman Syndrome/physiopathology  Case-Control Studies  Child  Delta Rhythm  Female  Gamma Rhythm  Humans  Male  Sleep Stages  Angelman syndrome  Biomarker  Coherence  eeg  Spindles  UBE3A Index. décimale : PER Périodiques Résumé : Background: Angelman syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, speech and motor impairments, epilepsy, abnormal sleep, and phenotypic overlap with autism. Individuals with AS display characteristic EEG patterns including high-amplitude rhythmic delta waves. Here, we sought to quantitatively explore EEG architecture in AS beyond known spectral power phenotypes. We were motivated by studies of functional connectivity and sleep spindles in autism to study these EEG readouts in children with AS. Methods: We analyzed retrospective wake and sleep EEGs from children with AS (age 4-11) and age-matched neurotypical controls. We assessed long-range and short-range functional connectivity by measuring coherence across multiple frequencies during wake and sleep. We quantified sleep spindles using automated and manual approaches. Results: During wakefulness, children with AS showed enhanced long-range EEG coherence across a wide range of frequencies. During sleep, children with AS showed increased long-range EEG coherence specifically in the gamma band. EEGs from children with AS contained fewer sleep spindles, and these spindles were shorter in duration than their neurotypical counterparts. Conclusions: We demonstrate two quantitative readouts of dysregulated sleep composition in children with AS-gamma coherence and spindles-and describe how functional connectivity patterns may be disrupted during wakefulness. Quantitative EEG phenotypes have potential as biomarkers and readouts of target engagement for future clinical trials and provide clues into how neural circuits are dysregulated in children with AS. En ligne : https://dx.doi.org/10.1186/s13229-018-0214-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371

Angelman syndrome: advancing the research frontier of neurodevelopmental disorders / Benjamin D. PHILPOT in Journal of Neurodevelopmental Disorders, 3-1 (March 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-1 (March 2011) . - p.50-6 Titre : Angelman syndrome: advancing the research frontier of neurodevelopmental disorders Type de document : texte imprimé Auteurs : Benjamin D. PHILPOT, Auteur ; Charlotte E. THOMPSON, Auteur ; Lisa FRANCO, Auteur ; Charles A. WILLIAMS, Auteur Article en page(s) : p.50-6 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : This report is a meeting summary of the 2010 Angelman Syndrome Foundation's scientific symposium on the neuroscience of UBE3A. Angelman syndrome is characterized by loss of speech, severe developmental delay, seizures, and ataxia. These core symptoms are caused by maternal allele disruptions of a single gene-UBE3A. UBE3A encodes an E3 ubiquitin ligase that targets certain proteins for proteasomal degradation. This biology has led to the expectation that the identification of Ube3a protein targets will lead to therapies for Angelman syndrome. The recent discovery of Ube3a substrates such as Arc (activity-regulated cytoskeletal protein) provides new insight into the mechanisms underlying the synaptic function and plasticity deficits caused by the loss of Ube3a. In addition to identifying Ube3a substrates, there have also been recent advances in understanding UBE3A's integrated role in the neuronal repertoire of genes and protein interactions. A developmental picture is now emerging whereby UBE3A gene dosage on chromosome 15 alters synaptic function, with deficiencies leading to Angelman syndrome and overexpression associated with classic autism symptomatology. En ligne : http://dx.doi.org/10.1007/s11689-010-9066-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] Angelman syndrome: advancing the research frontier of neurodevelopmental disorders [texte imprimé] / Benjamin D. PHILPOT, Auteur ; Charlotte E. THOMPSON, Auteur ; Lisa FRANCO, Auteur ; Charles A. WILLIAMS, Auteur . - p.50-6. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-1 (March 2011) . - p.50-6 Index. décimale : PER Périodiques Résumé : This report is a meeting summary of the 2010 Angelman Syndrome Foundation's scientific symposium on the neuroscience of UBE3A. Angelman syndrome is characterized by loss of speech, severe developmental delay, seizures, and ataxia. These core symptoms are caused by maternal allele disruptions of a single gene-UBE3A. UBE3A encodes an E3 ubiquitin ligase that targets certain proteins for proteasomal degradation. This biology has led to the expectation that the identification of Ube3a protein targets will lead to therapies for Angelman syndrome. The recent discovery of Ube3a substrates such as Arc (activity-regulated cytoskeletal protein) provides new insight into the mechanisms underlying the synaptic function and plasticity deficits caused by the loss of Ube3a. In addition to identifying Ube3a substrates, there have also been recent advances in understanding UBE3A's integrated role in the neuronal repertoire of genes and protein interactions. A developmental picture is now emerging whereby UBE3A gene dosage on chromosome 15 alters synaptic function, with deficiencies leading to Angelman syndrome and overexpression associated with classic autism symptomatology. En ligne : http://dx.doi.org/10.1007/s11689-010-9066-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

Characterization and structure-activity relationships of indenoisoquinoline-derived topoisomerase I inhibitors in unsilencing the dormant Ube3a gene associated with Angelman syndrome / Hyeong-Min LEE in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 45p. Titre : Characterization and structure-activity relationships of indenoisoquinoline-derived topoisomerase I inhibitors in unsilencing the dormant Ube3a gene associated with Angelman syndrome Type de document : texte imprimé Auteurs : Hyeong-Min LEE, Auteur ; Ellen P. CLARK, Auteur ; M. Bram KUIJER, Auteur ; Mark CUSHMAN, Auteur ; Yves POMMIER, Auteur ; Benjamin D. PHILPOT, Auteur Article en page(s) : 45p. Langues : Anglais (eng) Mots-clés : Angelman syndrome  Indenoisoquinoline  Indotecan  Topoisomerase I  Topoisomerase inhibitor  Topotecan  UBE3A Index. décimale : PER Périodiques Résumé : Background: Angelman syndrome (AS) is a severe neurodevelopmental disorder lacking effective therapies. AS is caused by mutations in ubiquitin protein ligase E3A (UBE3A), which is genomically imprinted such that only the maternally inherited copy is expressed in neurons. We previously demonstrated that topoisomerase I (Top1) inhibitors could successfully reactivate the dormant paternal allele of Ube3a in neurons of a mouse model of AS. We also previously showed that one such Top1 inhibitor, topotecan, could unsilence paternal UBE3A in induced pluripotent stem cell-derived neurons from individuals with AS. Although topotecan has been well-studied and is FDA-approved for cancer therapy, its limited CNS bioavailability will likely restrict the therapeutic use of topotecan in AS. The goal of this study was to identify additional Top1 inhibitors with similar efficacy as topotecan, with the expectation that these could be tested in the future for safety and CNS bioavailability to assess their potential as AS therapeutics. Methods: We tested 13 indenoisoquinoline-derived Top1 inhibitors to identify compounds that unsilence the paternal allele of Ube3a in mouse neurons. Primary cortical neurons were isolated from embryonic day 14.5 (E14.5) mice with a Ube3a-YFP fluorescent tag on the paternal allele (Ube3a(m+/pYFP) mice) or mice that lack the maternal Ube3a allele and hence model AS (Ube3a(m-/p+) mice). Neurons were cultured for 7 days, treated with drug for 72 h, and examined for paternal UBE3A protein expression by Western blot or fluorescence immunostaining. Dose responses of the compounds were determined across a log range of drug treatments, and cytotoxicity was tested using a luciferase-based assay. Results: All 13 indenoisoquinoline-derived Top1 inhibitors unsilenced paternal Ube3a. Several compounds exhibited favorable paternal Ube3a unsilencing properties, similar to topotecan, and of these, indotecan (LMP400) was the most effective based on estimated Emax (maximum response of unsilencing paternal Ube3a) and EC50 (half maximal effective concentration). Conclusions: We provide pharmacological profiles of indenoisoquinoline-derived Top1 inhibitors as paternal Ube3a unsilencers. All 13 tested compounds were effective at unsilencing paternal Ube3a, although with variable efficacy and potency. Indotecan (LMP400) demonstrated a better pharmacological profile of Ube3a unsilencing compared to our previous lead compound, topotecan. Taken together, indotecan and its structural analogues are potential AS therapeutics whose translational potential in AS treatment should be further assessed. En ligne : https://dx.doi.org/10.1186/s13229-018-0228-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 [article] Characterization and structure-activity relationships of indenoisoquinoline-derived topoisomerase I inhibitors in unsilencing the dormant Ube3a gene associated with Angelman syndrome [texte imprimé] / Hyeong-Min LEE, Auteur ; Ellen P. CLARK, Auteur ; M. Bram KUIJER, Auteur ; Mark CUSHMAN, Auteur ; Yves POMMIER, Auteur ; Benjamin D. PHILPOT, Auteur . - 45p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 45p. Mots-clés : Angelman syndrome  Indenoisoquinoline  Indotecan  Topoisomerase I  Topoisomerase inhibitor  Topotecan  UBE3A Index. décimale : PER Périodiques Résumé : Background: Angelman syndrome (AS) is a severe neurodevelopmental disorder lacking effective therapies. AS is caused by mutations in ubiquitin protein ligase E3A (UBE3A), which is genomically imprinted such that only the maternally inherited copy is expressed in neurons. We previously demonstrated that topoisomerase I (Top1) inhibitors could successfully reactivate the dormant paternal allele of Ube3a in neurons of a mouse model of AS. We also previously showed that one such Top1 inhibitor, topotecan, could unsilence paternal UBE3A in induced pluripotent stem cell-derived neurons from individuals with AS. Although topotecan has been well-studied and is FDA-approved for cancer therapy, its limited CNS bioavailability will likely restrict the therapeutic use of topotecan in AS. The goal of this study was to identify additional Top1 inhibitors with similar efficacy as topotecan, with the expectation that these could be tested in the future for safety and CNS bioavailability to assess their potential as AS therapeutics. Methods: We tested 13 indenoisoquinoline-derived Top1 inhibitors to identify compounds that unsilence the paternal allele of Ube3a in mouse neurons. Primary cortical neurons were isolated from embryonic day 14.5 (E14.5) mice with a Ube3a-YFP fluorescent tag on the paternal allele (Ube3a(m+/pYFP) mice) or mice that lack the maternal Ube3a allele and hence model AS (Ube3a(m-/p+) mice). Neurons were cultured for 7 days, treated with drug for 72 h, and examined for paternal UBE3A protein expression by Western blot or fluorescence immunostaining. Dose responses of the compounds were determined across a log range of drug treatments, and cytotoxicity was tested using a luciferase-based assay. Results: All 13 indenoisoquinoline-derived Top1 inhibitors unsilenced paternal Ube3a. Several compounds exhibited favorable paternal Ube3a unsilencing properties, similar to topotecan, and of these, indotecan (LMP400) was the most effective based on estimated Emax (maximum response of unsilencing paternal Ube3a) and EC50 (half maximal effective concentration). Conclusions: We provide pharmacological profiles of indenoisoquinoline-derived Top1 inhibitors as paternal Ube3a unsilencers. All 13 tested compounds were effective at unsilencing paternal Ube3a, although with variable efficacy and potency. Indotecan (LMP400) demonstrated a better pharmacological profile of Ube3a unsilencing compared to our previous lead compound, topotecan. Taken together, indotecan and its structural analogues are potential AS therapeutics whose translational potential in AS treatment should be further assessed. En ligne : https://dx.doi.org/10.1186/s13229-018-0228-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371

Comparative profiling of white matter development in the human and mouse brain reveals volumetric deficits and delayed myelination in Angelman syndrome / Ridthi K-R PATEL ; Tasmai VULLI ; Audrey L SMITH ; Martin A. STYNER ; Li-Ming HSU ; Sung-Ho LEE ; Yen-Yu Ian SHIH ; Heather C. HAZLETT ; Mark D. SHEN ; Alain C BURETTE ; Benjamin D. PHILPOT in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 54 Titre : Comparative profiling of white matter development in the human and mouse brain reveals volumetric deficits and delayed myelination in Angelman syndrome Type de document : texte imprimé Auteurs : Ridthi K-R PATEL, Auteur ; Tasmai VULLI, Auteur ; Audrey L SMITH, Auteur ; Martin A. STYNER, Auteur ; Li-Ming HSU, Auteur ; Sung-Ho LEE, Auteur ; Yen-Yu Ian SHIH, Auteur ; Heather C. HAZLETT, Auteur ; Mark D. SHEN, Auteur ; Alain C BURETTE, Auteur ; Benjamin D. PHILPOT, Auteur Article en page(s) : 54 Langues : Anglais (eng) Mots-clés : Animals  *Angelman Syndrome/genetics/pathology/diagnostic imaging  *White Matter/diagnostic imaging/pathology  Humans  Female  Male  Child, Preschool  *Myelin Sheath/metabolism/pathology  Infant  Child  Mice  *Ubiquitin-Protein Ligases/genetics/metabolism  Magnetic Resonance Imaging  Brain/diagnostic imaging/pathology/metabolism  Disease Models, Animal  Organ Size  Mice, Knockout  Microcephaly  Myelin basic protein  Myelination  Ube3a  White matter  and treatment of animals followed institutional and NIH guidelines, and all  animal use protocols were reviewed and approved by the UNC Institutional Animal  Care and Use Committee. Parents of AS and NT individuals provided informed  consent, and the institutional review board approved the research protocol.  Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman syndrome (AS), a severe neurodevelopmental disorder resulting from the loss of the maternal UBE3A gene, is marked by changes in the brain's white matter (WM). The extent of WM abnormalities seems to correlate with the severity of clinical symptoms, but these deficits are still poorly characterized or understood. This study provides the first large-scale measurement of WM volume reduction in children with AS. Furthermore, we probed the possibility of underlying WM neuropathology by examining the progression of myelination in an AS mouse model. METHODS: We conducted magnetic resonance imaging (MRI) on children with AS (n = 32) and neurotypical controls (n = 99) aged 0.5-12 years. In parallel, we examined myelination in postnatal Ube3a maternal-null mice (Ube3a(m-/p+); AS model), Ube3a paternal-null mice (Ube3a(m+/p-)), and wildtype controls (Ube3a(m+/p+)) using MRI, immunohistochemistry, western blotting, and electron microscopy. RESULTS: Our data revealed that AS individuals exhibit significant reductions in brain volume by ~ 1 year of age, and by 6-12 years of age WM is reduced by 26% and gray matter by 21%-approximately twice the reductions observed in the adult AS mouse model. Our AS mouse model saw a global delay in the onset of myelination, which normalized within days (likely corresponding to months or years in human development). This myelination delay is caused by the loss of UBE3A in neurons rather than UBE3A haploinsufficiency in oligodendrocytes. Interestingly, ultrastructural analyses did not reveal abnormalities in myelinated or unmyelinated axons. LIMITATIONS: It is difficult to extrapolate the timing and duration of the myelination delay observed in AS model mice to individuals with AS. CONCLUSIONS: This study reveals WM deficits as a hallmark in children with AS, demonstrating for the first time that these deficits are already apparent at 1 year of age. Parallel studies in a mouse model of AS show these deficits occur alongside the delayed onset of myelination, which results from the loss of neuronal (but not glial) UBE3A, though the causal relationship between these phenotypes remains to be determined. These findings emphasize the potential of WM as both a therapeutic target for interventions and a valuable biomarker for tracking the progression of AS and the effectiveness of potential treatments. En ligne : https://dx.doi.org/10.1186/s13229-024-00636-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555 [article] Comparative profiling of white matter development in the human and mouse brain reveals volumetric deficits and delayed myelination in Angelman syndrome [texte imprimé] / Ridthi K-R PATEL, Auteur ; Tasmai VULLI, Auteur ; Audrey L SMITH, Auteur ; Martin A. STYNER, Auteur ; Li-Ming HSU, Auteur ; Sung-Ho LEE, Auteur ; Yen-Yu Ian SHIH, Auteur ; Heather C. HAZLETT, Auteur ; Mark D. SHEN, Auteur ; Alain C BURETTE, Auteur ; Benjamin D. PHILPOT, Auteur . - 54. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 54 Mots-clés : Animals  *Angelman Syndrome/genetics/pathology/diagnostic imaging  *White Matter/diagnostic imaging/pathology  Humans  Female  Male  Child, Preschool  *Myelin Sheath/metabolism/pathology  Infant  Child  Mice  *Ubiquitin-Protein Ligases/genetics/metabolism  Magnetic Resonance Imaging  Brain/diagnostic imaging/pathology/metabolism  Disease Models, Animal  Organ Size  Mice, Knockout  Microcephaly  Myelin basic protein  Myelination  Ube3a  White matter  and treatment of animals followed institutional and NIH guidelines, and all  animal use protocols were reviewed and approved by the UNC Institutional Animal  Care and Use Committee. Parents of AS and NT individuals provided informed  consent, and the institutional review board approved the research protocol.  Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman syndrome (AS), a severe neurodevelopmental disorder resulting from the loss of the maternal UBE3A gene, is marked by changes in the brain's white matter (WM). The extent of WM abnormalities seems to correlate with the severity of clinical symptoms, but these deficits are still poorly characterized or understood. This study provides the first large-scale measurement of WM volume reduction in children with AS. Furthermore, we probed the possibility of underlying WM neuropathology by examining the progression of myelination in an AS mouse model. METHODS: We conducted magnetic resonance imaging (MRI) on children with AS (n = 32) and neurotypical controls (n = 99) aged 0.5-12 years. In parallel, we examined myelination in postnatal Ube3a maternal-null mice (Ube3a(m-/p+); AS model), Ube3a paternal-null mice (Ube3a(m+/p-)), and wildtype controls (Ube3a(m+/p+)) using MRI, immunohistochemistry, western blotting, and electron microscopy. RESULTS: Our data revealed that AS individuals exhibit significant reductions in brain volume by ~ 1 year of age, and by 6-12 years of age WM is reduced by 26% and gray matter by 21%-approximately twice the reductions observed in the adult AS mouse model. Our AS mouse model saw a global delay in the onset of myelination, which normalized within days (likely corresponding to months or years in human development). This myelination delay is caused by the loss of UBE3A in neurons rather than UBE3A haploinsufficiency in oligodendrocytes. Interestingly, ultrastructural analyses did not reveal abnormalities in myelinated or unmyelinated axons. LIMITATIONS: It is difficult to extrapolate the timing and duration of the myelination delay observed in AS model mice to individuals with AS. CONCLUSIONS: This study reveals WM deficits as a hallmark in children with AS, demonstrating for the first time that these deficits are already apparent at 1 year of age. Parallel studies in a mouse model of AS show these deficits occur alongside the delayed onset of myelination, which results from the loss of neuronal (but not glial) UBE3A, though the causal relationship between these phenotypes remains to be determined. These findings emphasize the potential of WM as both a therapeutic target for interventions and a valuable biomarker for tracking the progression of AS and the effectiveness of potential treatments. En ligne : https://dx.doi.org/10.1186/s13229-024-00636-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555

Deficits in higher visual area representations in a mouse model of Angelman syndrome / Leah B. TOWNSEND in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Deficits in higher visual area representations in a mouse model of Angelman syndrome Type de document : texte imprimé Auteurs : Leah B. TOWNSEND, Auteur ; Kelly A. JONES, Auteur ; Christopher R. DORSETT, Auteur ; Benjamin D. PHILPOT, Auteur ; Spencer L. SMITH, Auteur Langues : Anglais (eng) Mots-clés : Angelman Syndrome/genetics  Animals  Disease Models, Animal  Mice  Neurons  Visual Cortex Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory processing deficits are common in individuals with neurodevelopmental disorders. One hypothesis is that deficits may be more detectable in downstream, "higher" sensory areas. A mouse model of Angelman syndrome (AS), which lacks expression of the maternally inherited Ube3a allele, has deficits in synaptic function and experience-dependent plasticity in the primary visual cortex. Thus, we hypothesized that AS model mice have deficits in visually driven neuronal responsiveness in downstream higher visual areas (HVAs). METHODS: Here, we used intrinsic signal optical imaging and two-photon calcium imaging to map visually evoked neuronal activity in the primary visual cortex and HVAs in response to an array of stimuli. RESULTS: We found a highly specific deficit in HVAs. Drifting gratings that changed speed caused a strong response in HVAs in wildtype mice, but this was not observed in littermate AS model mice. Further investigation with two-photon calcium imaging revealed the effect to be largely driven by aberrant responses of inhibitory interneurons, suggesting a cellular basis for higher level, stimulus-selective cortical dysfunction in AS. CONCLUSION: Assaying downstream, or "higher" circuitry may provide a more sensitive measure for circuit dysfunction in mouse models of neurodevelopmental disorders. TRIAL REGISTRATION: Not applicable. En ligne : https://dx.doi.org/10.1186/s11689-020-09329-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Deficits in higher visual area representations in a mouse model of Angelman syndrome [texte imprimé] / Leah B. TOWNSEND, Auteur ; Kelly A. JONES, Auteur ; Christopher R. DORSETT, Auteur ; Benjamin D. PHILPOT, Auteur ; Spencer L. SMITH, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Angelman Syndrome/genetics  Animals  Disease Models, Animal  Mice  Neurons  Visual Cortex Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory processing deficits are common in individuals with neurodevelopmental disorders. One hypothesis is that deficits may be more detectable in downstream, "higher" sensory areas. A mouse model of Angelman syndrome (AS), which lacks expression of the maternally inherited Ube3a allele, has deficits in synaptic function and experience-dependent plasticity in the primary visual cortex. Thus, we hypothesized that AS model mice have deficits in visually driven neuronal responsiveness in downstream higher visual areas (HVAs). METHODS: Here, we used intrinsic signal optical imaging and two-photon calcium imaging to map visually evoked neuronal activity in the primary visual cortex and HVAs in response to an array of stimuli. RESULTS: We found a highly specific deficit in HVAs. Drifting gratings that changed speed caused a strong response in HVAs in wildtype mice, but this was not observed in littermate AS model mice. Further investigation with two-photon calcium imaging revealed the effect to be largely driven by aberrant responses of inhibitory interneurons, suggesting a cellular basis for higher level, stimulus-selective cortical dysfunction in AS. CONCLUSION: Assaying downstream, or "higher" circuitry may provide a more sensitive measure for circuit dysfunction in mouse models of neurodevelopmental disorders. TRIAL REGISTRATION: Not applicable. En ligne : https://dx.doi.org/10.1186/s11689-020-09329-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Delayed loss of UBE3A reduces the expression of Angelman syndrome-associated phenotypes / Monica SONZOGNI in Molecular Autism, 10 (2019)  

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Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis / Michael S. SIDOROV in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

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Erratum to: Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis / Michael S. SIDOROV in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

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Evaluation of electroencephalography biomarkers for Angelman syndrome during overnight sleep / Yuval LEVIN in Autism Research, 15-6 (June 2022)  

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Sleep EEG signatures in mouse models of 15q11.2-13.1 duplication (Dup15q) syndrome / Vidya SARAVANAPANDIAN in Journal of Neurodevelopmental Disorders, 16 (2024)  

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A small-molecule screen reveals novel modulators of MeCP2 and X-chromosome inactivation maintenance / Hyeong-Min LEE in Journal of Neurodevelopmental Disorders, 12 (2020)  

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Subcellular organization of UBE3A in human cerebral cortex / Alain C BURETTE in Molecular Autism, 9 (2018)  

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