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

Genotype- and sex-dependent effects of altered Cntnap2 expression on the function of visual cortical areas / Leah B. TOWNSEND in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.2 Titre : Genotype- and sex-dependent effects of altered Cntnap2 expression on the function of visual cortical areas Type de document : texte imprimé Auteurs : Leah B. TOWNSEND, Auteur ; Spencer L. SMITH, Auteur Article en page(s) : p.2 Langues : Anglais (eng) Mots-clés : Autism  Cortical circuits  Higher visual areas  Intrinsic signal optical imaging  Mouse models  Sex Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a heritable, heterogeneous neurodevelopmental disorder that is four times more likely to affect males than females. Despite this overt sex bias, it is unclear how genetic mutations associated with ASD alter cortical circuitry to produce the behavioral phenotypes by which ASD is diagnosed. Contactin-associated protein-like 2 (CNTNAP2) is an ASD-associated gene, and while Cntnap2 knockout (KO) mice recapitulate many of the features of ASD, the effect on cortical circuitry is poorly understood. Moreover, although heterozygous (Het) mice are the more relevant genotype for ASD-linked CNTNAP2 mutations in humans, to our knowledge, no effects in Het mice have been previously reported. METHODS: Intrinsic signal optical imaging was used to measure functional visual responses in primary and higher visual cortical areas in male and female Cntnap2 KO, Het, and wild-type (WT) mice. Main effect of genotype was assessed with one-way ANOVA. Visual responses were also measured in P17-18 and P30-32 KO and WT mice. Main effects of age and genotype were assessed using two-way ANOVA. RESULTS: Visually evoked activity in dorsal stream associated higher visual areas in both KO and Het adult males was decreased relative to WT adult males. This decrease was not observed in adult females. Additionally, no significant difference was observed between WT and KO males at P17-18 with differences beginning to emerge at P30-32. CONCLUSIONS: The functional responses of cortical circuitry in male mice are more strongly affected by Cntnap2 mutations than females, an effect present even in Hets. The observed differences in males emerge with development beginning at P30-32. These results reveal genotype- and sex-dependent effects of altered Cntnap2 expression and can shed light on the sex-dependent incidence of ASD. En ligne : http://dx.doi.org/10.1186/s11689-016-9182-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Genotype- and sex-dependent effects of altered Cntnap2 expression on the function of visual cortical areas [texte imprimé] / Leah B. TOWNSEND, Auteur ; Spencer L. SMITH, Auteur . - p.2. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.2 Mots-clés : Autism  Cortical circuits  Higher visual areas  Intrinsic signal optical imaging  Mouse models  Sex Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a heritable, heterogeneous neurodevelopmental disorder that is four times more likely to affect males than females. Despite this overt sex bias, it is unclear how genetic mutations associated with ASD alter cortical circuitry to produce the behavioral phenotypes by which ASD is diagnosed. Contactin-associated protein-like 2 (CNTNAP2) is an ASD-associated gene, and while Cntnap2 knockout (KO) mice recapitulate many of the features of ASD, the effect on cortical circuitry is poorly understood. Moreover, although heterozygous (Het) mice are the more relevant genotype for ASD-linked CNTNAP2 mutations in humans, to our knowledge, no effects in Het mice have been previously reported. METHODS: Intrinsic signal optical imaging was used to measure functional visual responses in primary and higher visual cortical areas in male and female Cntnap2 KO, Het, and wild-type (WT) mice. Main effect of genotype was assessed with one-way ANOVA. Visual responses were also measured in P17-18 and P30-32 KO and WT mice. Main effects of age and genotype were assessed using two-way ANOVA. RESULTS: Visually evoked activity in dorsal stream associated higher visual areas in both KO and Het adult males was decreased relative to WT adult males. This decrease was not observed in adult females. Additionally, no significant difference was observed between WT and KO males at P17-18 with differences beginning to emerge at P30-32. CONCLUSIONS: The functional responses of cortical circuitry in male mice are more strongly affected by Cntnap2 mutations than females, an effect present even in Hets. The observed differences in males emerge with development beginning at P30-32. These results reveal genotype- and sex-dependent effects of altered Cntnap2 expression and can shed light on the sex-dependent incidence of ASD. En ligne : http://dx.doi.org/10.1186/s11689-016-9182-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

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