Prefrontal cortex (PFC) is highly influenced by the inputs from ventral tegmental area (VTA); however, how the projection from VTA impacts PFC neurons and how the synaptically released dopamine affects PFC activity are largely unclear. Using optogenetics and electrophysiological approaches, we examined the impact of VTA stimulation on PFC principal neurons and parvalbumin-positive (PV+) interneurons and the modulatory role of dopamine. We found that the brief activation of the VTA–PFC circuit immediately induced action potential firing, which was mediated by glutamatergic transmission. However, strong stimulation of VTA gradually induced a marked and prolonged enhancement of the excitability of PFC PV+ interneurons and a modest and short-lived enhancement of the excitability of PFC principal neurons. Blocking dopamine receptors (DARs) shortened the VTA excitation of PFC PV+ interneurons and prolonged the VTA excitation of PFC principal neurons. Blocking GABA_A receptors induced a similar effect as DAR antagonists in PFC principal neurons, suggesting that the dopaminergic effect is through influencing the inhibitory transmission system. These results have revealed a role of dopamine in regulating the temporal dynamics of excitation/inhibition balance in VTA–PFC circuit, which provides insights into the functional consequence of activating dopamine system in the mesocortical system.

中文翻译：

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多巴胺差异调节前额皮质主要神经元和中间神经元对腹侧被盖区输入的光遗传学刺激的反应动力学。

前额叶皮层 (PFC) 受腹侧被盖区 (VTA) 输入的影响很大；然而，VTA 的投射如何影响 PFC 神经元以及突触释放的多巴胺如何影响 PFC 活动在很大程度上尚不清楚。我们使用光遗传学和电生理学方法研究了 VTA 刺激对 PFC 主神经元和小清蛋白阳性 (PV+) 中间神经元的影响以及多巴胺的调节作用。我们发现 VTA-PFC 电路的短暂激活会立即诱导动作电位激发，这是由谷氨酸能传递介导的。然而，VTA 的强烈刺激逐渐引起 PFC PV+ 中间神经元兴奋性的显着和长期增强，以及 PFC 主神经元兴奋性的适度和短暂的增强。阻断多巴胺受体 (DAR) 会缩短 PFC PV+ 中间神经元的 VTA 激发并延长 PFC 主要神经元的 VTA 激发。阻断 GABA_A受体在 PFC 主要神经元中诱导了与 DAR 拮抗剂类似的作用，表明多巴胺能作用是通过影响抑制性传递系统。这些结果揭示了多巴胺在调节 VTA-PFC 电路中兴奋/抑制平衡的时间动态中的作用，这提供了对激活中皮层系统中多巴胺系统的功能后果的见解。