RT Journal Article SR Electronic T1 Reduced Vglut2/Slc17a6 Gene Expression Levels throughout the Mouse Subthalamic Nucleus Cause Cell Loss and Structural Disorganization Followed by Increased Motor Activity and Decreased Sugar Consumption JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0264-16.2016 DO 10.1523/ENEURO.0264-16.2016 VO 3 IS 5 A1 Nadine Schweizer A1 Thomas Viereckel A1 Casey J.A. Smith-Anttila A1 Karin Nordenankar A1 Emma Arvidsson A1 Souha Mahmoudi A1 André Zampera A1 Hanna Wärner Jonsson A1 Jonas Bergquist A1 Daniel Lévesque A1 Åsa Konradsson-Geuken A1 Malin Andersson A1 Sylvie Dumas A1 Åsa Wallén-Mackenzie YR 2016 UL http://www.eneuro.org/content/3/5/ENEURO.0264-16.2016.abstract AB The subthalamic nucleus (STN) plays a central role in motor, cognitive, and affective behavior. Deep brain stimulation (DBS) of the STN is the most common surgical intervention for advanced Parkinson’s disease (PD), and STN has lately gained attention as target for DBS in neuropsychiatric disorders, including obsessive compulsive disorder, eating disorders, and addiction. Animal studies using STN-DBS, lesioning, or inactivation of STN neurons have been used extensively alongside clinical studies to unravel the structural organization, circuitry, and function of the STN. Recent studies in rodent STN models have exposed different roles for STN neurons in reward-related functions. We have previously shown that the majority of STN neurons express the vesicular glutamate transporter 2 gene (Vglut2/Slc17a6) and that reduction of Vglut2 mRNA levels within the STN of mice [conditional knockout (cKO)] causes reduced postsynaptic activity and behavioral hyperlocomotion. The cKO mice showed less interest in fatty rewards, which motivated analysis of reward-response. The current results demonstrate decreased sugar consumption and strong rearing behavior, whereas biochemical analyses show altered dopaminergic and peptidergic activity in the striatum. The behavioral alterations were in fact correlated with opposite effects in the dorsal versus the ventral striatum. Significant cell loss and disorganization of the STN structure was identified, which likely accounts for the observed alterations. Rare genetic variants of the human VGLUT2 gene exist, and this study shows that reduced Vglut2/Slc17a6 gene expression levels exclusively within the STN of mice is sufficient to cause strong modifications in both the STN and the mesostriatal dopamine system.