Stimulus-driven cortical circuit deficits in a mouse model of Angelman Syndrome

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

? DESCRIPTION (provided by applicant): Angelman Syndrome (AS) is a severe neurodevelopmental disorder characterized by developmental delay, profound speech impairment, movement and balance disorders, seizures, and enhanced sensitivity to sensory inputs. AS is caused by deficient expression or function of the maternally inherited UBE3A allele. The cortex is critical for sensory processing and cognition, both of which are deficient in AS. Defects in synaptic and cortical plasticity have been previously shown in mouse models of AS, however the functional consequences of these pathologies at the level of cortical circuitry remains unknown; understanding the effects of maternal Ube3a loss on developing cortex will be pivotal in the development of effective treatments. The studies in this proposal will address this knowledge gap by testing the hypothesis that maternal Ube3a loss alters the developmental refinement of cortical circuitry within mouse visual cortex to produce deficient functional responses and altered neuronal selectivity. Aim 1 will use intrinsic signal optical imaging to identify in vivo when and how loss of maternal Ube3a changes cortical responsiveness to visual stimuli. Aim 2 will use 2-photon population calcium imaging to investigate when and how neuronal properties that give rise to the unique visual processing characteristics in different regions of mouse visual cortex are altered in the absence of maternal Ube3a. This project utilizes state-of-the-art in vivo imaging techniques to characterize the functional effects of maternal Ube3a loss on the development of cortical circuitry, the results of which will be instrumental in determining when and how to intervene to best treat this syndrome.