Deficits in higher visual area representations in a mouse model of Angelman syndrome
Abstract 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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | Journal of Neurodevelopmental Disorders |
| Online Access: | http://link.springer.com/article/10.1186/s11689-020-09329-y |
| _version_ | 1811223463635976192 |
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| author | Leah B. Townsend Kelly A. Jones Christopher R. Dorsett Benjamin D. Philpot Spencer L. Smith |
| author_facet | Leah B. Townsend Kelly A. Jones Christopher R. Dorsett Benjamin D. Philpot Spencer L. Smith |
| author_sort | Leah B. Townsend |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-12T08:33:18Z |
| format | Article |
| id | doaj.art-c228e2076f6a4eaca4362e477f72d151 |
| institution | Directory Open Access Journal |
| issn | 1866-1947 1866-1955 |
| language | English |
| last_indexed | 2024-04-12T08:33:18Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neurodevelopmental Disorders |
| spelling | doaj.art-c228e2076f6a4eaca4362e477f72d1512022-12-22T03:40:07ZengBMCJournal of Neurodevelopmental Disorders1866-19471866-19552020-10-0112111410.1186/s11689-020-09329-yDeficits in higher visual area representations in a mouse model of Angelman syndromeLeah B. Townsend0Kelly A. Jones1Christopher R. Dorsett2Benjamin D. Philpot3Spencer L. Smith4Neuroscience Curriculum, University of North Carolina School of MedicineNeuroscience Curriculum, University of North Carolina School of MedicineNeuroscience Curriculum, University of North Carolina School of MedicineNeuroscience Curriculum, University of North Carolina School of MedicineDepartment of Electrical & Computer Engineering, Neuroscience Research Institute, Center for BioEngineering, University of California Santa BarbaraAbstract 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.http://link.springer.com/article/10.1186/s11689-020-09329-y |
| spellingShingle | Leah B. Townsend Kelly A. Jones Christopher R. Dorsett Benjamin D. Philpot Spencer L. Smith Deficits in higher visual area representations in a mouse model of Angelman syndrome Journal of Neurodevelopmental Disorders |
| title | Deficits in higher visual area representations in a mouse model of Angelman syndrome |
| title_full | Deficits in higher visual area representations in a mouse model of Angelman syndrome |
| title_fullStr | Deficits in higher visual area representations in a mouse model of Angelman syndrome |
| title_full_unstemmed | Deficits in higher visual area representations in a mouse model of Angelman syndrome |
| title_short | Deficits in higher visual area representations in a mouse model of Angelman syndrome |
| title_sort | deficits in higher visual area representations in a mouse model of angelman syndrome |
| url | http://link.springer.com/article/10.1186/s11689-020-09329-y |
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