There is an ongoing debate on the contribution of the neuronal glutamate transporter EAAC1 to the onset of compulsive behaviors. Here, we used behavioral, electrophysiological, molecular, and viral approaches in male and female mice to identify the molecular and cellular mechanisms by which EAAC1 controls the execution of repeated motor behaviors. Our findings show that, in the striatum, a brain region implicated with movement execution, EAAC1 limits group I metabotropic glutamate receptor (mGluRI) activation, facilitates D1 dopamine receptor (D1R) expression, and ensures long-term synaptic plasticity. Blocking mGluRI in slices from mice lacking EAAC1 restores D1R expression and synaptic plasticity. Conversely, activation of intracellular signaling pathways coupled to mGluRI in D1R-containing striatal neurons of mice expressing EAAC1 leads to reduced D1R protein level and increased stereotyped movement execution. These findings identify new molecular mechanisms by which EAAC1 can shape glutamatergic and dopaminergic signals and control repeated movement execution.
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Scimemi, Annalisa; Bellini, Stefania; Fleming, Kelsey E.; De, Modhurika; McCauley, John P.; Petroccione, Maurice A.; D'Brant, Lianna Y.; Tkachenko, Artem; Kwon, SoYoung; and Jones, Lindsey A., "Neuronal Glutamate Transporters Control Dopaminergic Signaling and Compulsive Behaviors" (2018). Biological Sciences Faculty Scholarship. 36.