EXECUTIVE DYSFUNCTIONS IN THE EAAT3 OVEREXPRESSING MOUSE MODEL OF COMPULSIVE BEHAVIOR

Executive functions govern behavior and adapt to changing demands. In neuropsychiatric disorders like obsessive-compulsive disorder, these functions often suffer impairments. Mice that overproduce the neuronal glutamate transporter EAAT3 in the brain (EAAT3glo/CaMKII) display heightened compulsive behaviors and brain changes akin to OCD.

However, scientists have yet to determine whether EAAT3 overexpression impacts executive functioning across various cognitive areas. To address this, researchers evaluated EAAT3glo/CaMKII mice using tasks that measure three cognitive domains considered part of executive function: cognitive flexibility, working memory, and inhibitory control.

The mice exhibited impaired cognitive flexibility, struggling in both operant extinction and reversal learning tasks. They also failed to learn the Trial-unique, delayed nonmatching-to-location task, indicating potential working memory issues. Additionally, EAAT3glo/CaMKII mice displayed increased impulsivity in the five-choice serial reaction time task, as shown by a higher number of premature responses. However, their perseverative responses, accuracy of responses, and attentional performance were not affected.

Overall, these results suggest that overexpression of EAAT3 in forebrain neurons leads to a cognitive profile marked by difficulties in flexibility and task acquisition, alongside heightened impulsivity. Importantly, attentional performance and motivational measures remain unaffected in these mice, providing insight into a model of compulsive behavior.