Mouse model of Angelman syndrome exhibits reduced retinal activity during development

Angelman Syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, seizures, and motor dysfunction caused by loss of function of the maternal UBE3A allele. A large proportion of patients exhibit visual impairments, but the underlying circuit-level mechanisms are not well understood. Spontaneous retinal waves provide essential patterned activity that guides the wiring and refinement of retinofugal projections to visual brain centers during a critical early developmental window. Here, using high-density microelectrode array recordings from postnatal day 8, 11 mouse retinas, we demonstrate that Ube3a deficiency leads to reduced retinal ganglion cell (RGC) firing rates and fewer retinal waves while largely preserving retinal wave propagation properties. The reduced activity levels observed in AS retinas represent a novel finding that may help explain how Ube3a deficiency disrupts the normal activity-dependent refinement of developing neural circuits.