Deficits in higher visual area representations in a mouse model of Angelman syndrome
- PDF / 2,003,212 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 49 Downloads / 182 Views
(2020) 12:28
RESEARCH
Open Access
Deficits in higher visual area representations in a mouse model of Angelman syndrome Leah B. Townsend1, Kelly A. Jones1,2, Christopher R. Dorsett1, Benjamin D. Philpot1,2,3,4 and Spencer L. Smith5*
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 twophoton 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.
Introduction Copy number variants in the UBE3A gene, which encodes an E3 ubiquitin ligase, result in neurodevelopmental disorders in humans. Loss of UBE3A in neurons underlies Angelman syndrome (AS) [1, 2], and increased UBE3A gene dosage via duplications is associated with autism [3–5]. AS is characterized by developmental delays, speech impairments, movement and balance disorders, seizures, and an apparent happy demeanor [6]. Sensory processing abnormalities are also common * Correspondence: [email protected] 5 Department of Electrical & Computer Engineering, Neuroscience Research Institute, Center for BioEngineering, University of California Santa Barbara, 2002 BioEngineering Building; Mail code 5100, Santa Barbara, CA 93106-5100, USA Full list of author information is available at the end of the article
in individuals affected with AS, including hyper- and hypo-responsivity to visual stimuli [7–9]. Because the paternal allele of UBE3A is epigenetically silenced in most neurons [10–14], deficient expression or function of the maternally inherited UBE3A allele alone is detrimental and causes AS [1, 15]. Mouse models of AS, which lack maternal Ube3a expression, recapitulate many of the phenotypes of AS including seizures, movement and balance deficits, and learning deficits [16–18]. In humans, loss of maternal UBE3A produces symptoms that emerge during development, such that individuals with AS often go undiagnosed until 6–12
Data Loading...
