Thesis Defense Announcement

College of Arts and Sciences announces the Final Thesis Defense of

Hunter Nolen

for the Degree of Master of Science

July 17, 2019 at 9:00 AM Psychology Building,Room 208

Advisor: Helen Sable

Impulsivity in the ADGRL3 (LPHN3) Knockout Rodent: Relevance to Attention-Deficit/Hyperactivity Disorder

ABSTRACT:Children diagnosed with attention-deficit hyperactivity disorder (ADHD) often suffer from symptoms such as motor impulsivity, attentional regulation impairments, and deficits in working memory which make the navigation of many novel, real-world scenarios particularly cumbersome. Evidence gathered from neuroimaging studies in humans, neuromolecular studies in animal models for ADHD, and the neuropsychopharmacology of the most effective medications used to treat ADHD systematically suggest the pathophysiology that characterizes this disorder is driven by abnormally depleted extracellular levels of dopamine (DA) within the medial prefrontal cortex (mPFC). A number of studies have shown that an attenuated expression of latrophilin 3 (Lphn3) gene is linked to several alterations in DA activity that likely lead to a dampening of extracellular DA levels that is both temporally and spatially consistent with the ADHD pathology expressed in humans. Importantly, disruptions in DA transmission that have been suggested to occur as a result of Lphn3 variation have also been accompanied by behavioral deficits that closely mirror those that are observed in humans suffering from ADHD. Despite the abundance of previous research that exists on ADHD in both human participants and from animal models, extant research that offers a systematic and comprehensive investigation of executive function in an Lphn3 variant model is lacking making the precise behavioral impairments that might occur as a result of differential Lphn3 expression unknown. As such, the present study aims to employ two different operant inhibitory control tasks (including differential reinforcement of low rates and delay discounting) in an effort to offer a more explicit and complete assessment of the influence of Lphn3 variation on mPFC-dependent executive function in a rodent model of ADHD.