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At this time, little is known regarding the regulation of the development of the two compartments.<jats:italic>Nr4a1<\/jats:italic>, primarily described as a nuclear receptor\/immediate early gene involved in the homeostasis of the dopaminergic system, is a striosomal marker. Using<jats:italic>Nr4a1<\/jats:italic>-overexpressing and<jats:italic>Nr4a1<\/jats:italic>-null mice, we sought to determine whether Nr4a1 is necessary and\/or sufficient for striosome development. We report that<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro<\/jats:italic>,<jats:italic>Nr4a1<\/jats:italic>and<jats:italic>Oprm1<\/jats:italic>mRNA levels are correlated. In the absence of Nr4a, there is a decrease in the percentage of striatal surface area occupied by striosomes. Alterations in<jats:italic>Nr4a1<\/jats:italic>expression leads to dysregulation of multiple mRNAs of members of the dopamine receptor D<jats:sub>1<\/jats:sub>signal transduction system. Constitutive overexpression of<jats:italic>Nr4a1<\/jats:italic>decreases both the induction of phosphorylation of ERK after a single cocaine exposure and locomotor sensitization following chronic cocaine exposure.<jats:italic>Nr4a1<\/jats:italic>overexpression increases MSN excitability but reduces MSN long-term potentiation. In the resting state, type 5 adenylyl cyclase (AC5) activity is normal, but the ability of AC5 to be activated by Drd1 G-protein-coupled receptor inputs is decreased. Our results support a role for<jats:italic>Nr4a1<\/jats:italic>in determination of striatal patch\/matrix structure and in regulation of dopaminoceptive neuronal function.<\/jats:p>","DOI":"10.1523\/eneuro.0305-19.2019","type":"journal-article","created":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T21:45:17Z","timestamp":1569015917000},"page":"ENEURO.0305-19.2019","source":"Crossref","is-referenced-by-count":23,"title":["Nuclear Receptor Nr4a1 Regulates Striatal Striosome Development and Dopamine D<sub>1<\/sub>Receptor 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