Angelman Syndrome (AS) is a rare genetic neurodevelopmental disorder characterized by intellectual disabilities, motor and balance deficits, impaired communication, and a happy, excitable demeanor with frequent laughter. We sought to elucidate a preclinical outcome measure in male and female rats that addressed communication abnormalities of AS and other neurodevelopmental disorders in which communication is atypical and/or lack of speech is a core feature. We discovered, and herein report for the first time, excessive laughter-like 50-kHz ultrasonic emissions in the Ube3a mat-/pat+ rat model of AS, which suggests an excitable, playful demeanor and elevated positive affect, similar to the demeanor of individuals with AS. Also in line with the AS phenotype, Ube3a mat-/pat+ rats demonstrated aberrant social interactions with a novel partner, distinctive gait abnormalities, impaired cognition, an underlying long-term potentiation deficit, and profound reductions in brain volume. These unique, robust phenotypes provide advantages compared to currently available mouse models and will be highly valuable as outcome measures in the evaluation of therapies for AS.SIGNIFICANCE STATEMENTAngelman Syndrome (AS) is a severe neurogenetic disorder for which there is no cure, despite decades of research using mouse models. This study utilized a recently developed rat model of AS to delineate disease-relevant outcome measures in order to facilitate therapeutic development. We found the rat to be a strong model of AS, offering several advantages over mouse models by exhibiting numerous AS-relevant phenotypes including overabundant laughter-like vocalizations, reduced hippocampal long-term potentiation, and volumetric anomalies across the brain. These findings are unconfounded by detrimental motor abilities and background strain, issues plaguing mouse models. This rat model represents an important advancement in the field of AS and the outcome metrics reported herein will be central to the therapeutic pipeline.