Dopaminergic modulation of corticostriatal transmission is critically involved in reward-driven behaviors. This modulation is mainly mediated by dopamine D1 receptors (D1Rs) and D2Rs, which are highly expressed in medium spiny neurons (MSNs) of the dorsomedial striatum (DMS), a brain region essential for goal-directed behaviors and addiction. D1Rs and D2Rs are also present at presynaptic cortical terminals within the DMS. However, it is not known how addictive substances alter the glutamatergic strength of striatal synapses expressing presynaptic dopamine receptors. Using cell type-specific Cre mice in combination with optogenetic techniques, we measured glutamatergic transmission at D1R- or D2R-expressing afferents to DMS MSNs. We found larger excitatory postsynaptic currents at the synapses between the extra-striatal D2R-expressing afferents and D1R-expressing MSNs (D2→D1), as compared with those observed at the other tested synapses (D1→D1, D1→D2, and D2→D2). Additionally, excessive alcohol consumption induced a long-lasting potentiation of glutamatergic transmission at the corticostriatal D2→D1 synapse. Furthermore, we demonstrated that activation of postsynaptic, but not presynaptic, D2Rs inhibited corticostriatal transmission in an endocannabinoid-dependent manner. Taken together, these data provide detailed information on the mechanisms underlying dopamine receptor-mediated modulation of brain reward circuitry.

中文翻译：

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饮酒会增强谷氨酸能从表达D2受体的传入神经传递到背部纹状体中表达D1受体的中等多刺神经元。

皮质上皮传递的多巴胺能调节与奖励驱动的行为密切相关。这种调节主要是由多巴胺D1受体（D1Rs）和D2Rs介导的，它们在背纹状体（DMS）的中突棘神经元（MSNs）中高度表达，这是目标定向行为和成瘾必不可少的大脑区域。D1R和D2R也​​存在于DMS内的突触前皮质末端。然而，尚不知道成瘾性物质如何改变表达突触前多巴胺受体的纹状体突触的谷氨酸能强度。使用细胞类型特异性Cre小鼠与光遗传学技术相结合，我们测量了DMS MSNs的D1R或D2R表达传入子的谷氨酸能传递。与其他测试突触（D1→D1，D1→D2和D2）相比，我们发现在纹状体外表达D2R的传入神经和表达D1R的MSN（D2→D1）之间的突触中有更大的兴奋性突触后电流。 →D2）。此外，过量饮酒会导致皮质口D2→D1突触处的谷氨酸能传递持续增强。此外，我们证明了激活突触后，但不是突触前，D2Rs以依赖内源性大麻素的方式抑制皮质类固醇的传播。综上所述，这些数据提供了有关多巴胺受体介导的大脑奖赏电路调节机制的详细信息。过量饮酒会导致皮质二尖瓣D2→D1突触处的谷氨酸能传递持续增强。此外，我们证明了激活突触后，但不是突触前，D2Rs以依赖内源性大麻素的方式抑制皮质类固醇的传播。综上所述，这些数据提供了有关多巴胺受体介导的大脑奖赏电路调节机制的详细信息。过量饮酒会导致皮质二尖瓣D2→D1突触处的谷氨酸能传递持续增强。此外，我们证明了激活突触后，但不是突触前，D2Rs以依赖内源性大麻素的方式抑制皮质类固醇的传播。综上所述，这些数据提供了有关多巴胺受体介导的大脑奖赏电路调节机制的详细信息。