Neuronal Glutamate Transporters Control Dopaminergic Signaling and Compulsive Behaviors

• DOI: 10.1523/jneurosci.1906-17.2017
• Publication Date: 2017-12-11T15:45:18Z
• Authors: Stefania Bellini; Kelsey E. Fleming; Modhurika De; John P. McCauley; Maurice A. Petroc...; Lianna Y. D'Brant; Artem Tkachenko; SoYoung Kwon; Lindsey A. Jones; Annalisa Scimemi
• Keywords: Male; Mice, Knockout; 0301 basic medicine; 0303 health sciences; Neuronal Plasticity; striatum; Dopamine; Receptors, Dopamine D1; glutamate; Receptors, Metabotropic Glutamate; Corpus Striatum; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Excitatory Amino Acid Transporter 3; transporter; mGluR; Compulsive Behavior; synaptic transmission; Animals; Female; dopamine; Signal Transduction

There is an ongoing debate on the contribution of neuronal glutamate transporter EAAC1 to onset compulsive behaviors. Here, we used behavioral, electrophysiological, molecular, and viral approaches in male female mice identify molecular cellular mechanisms by which controls execution repeated motor Our findings show that, striatum, a brain region implicated with movement execution, limits group I metabotropic receptor (mGluRI) activation, facilitates D1 dopamine (D1R) expression, ensures long-term synaptic plasticity. Blocking mGluRI slices from lacking restores D1R expression Conversely, activation intracellular signaling pathways coupled D1R-containing striatal neurons expressing leads reduced protein level increased stereotyped execution. These new can shape glutamatergic dopaminergic signals control SIGNIFICANCE STATEMENT Genetic studies implicate Slc1a1 , gene encoding EAAC1, obsessive-compulsive disorder (OCD). abundantly expressed that hyperactive OCD. What remains unknown how shapes function striatum. receptors (mGluRIs) striatum and, doing so, promotes expression. Targeted cascades mGluRIs reduces triggers provide information basis OCD suggest avenues for its treatment.