Dopamine (DA) acts as a key regulator in controlling emotion, and dysfunction of DA signal has been implicated in the pathophysiology of some psychiatric disorders, including anxiety. Ventral tegmental area (VTA) is one of main regions with DA-producing neurons. VTA DAergic projections in mesolimbic brain regions play a crucial role in regulating anxiety-like behaviors, however, the function of DA signal within VTA in regulating emotion remains unclear. Here, we observe that pharmacological activation/inhibition of VTA D1 receptors will alleviate/aggravate mouse anxiety-like behaviors, and knockdown of VTA D1 receptor expression also exerts anxiogenic effect. With fluorescence in situ hybridization and electrophysiological recording, we find that D1 receptors are functionally expressed in VTA neurons. Silencing/activating VTA D1 neurons bidirectionally modulate mouse anxiety-like behaviors. Furthermore, knocking down D1 receptors in VTA DA and glutamate neurons elevates anxiety-like state, but in GABA neurons has the opposite effect. In addition, we identify the glutamatergic projection from VTA D1 neurons to lateral septum is mainly responsible for the anxiolytic effect induced by activating VTA D1 neurons. Thus, our study not only characterizes the functional expression of D1 receptors in VTA neurons, but also uncovers the pivotal role of DA signal within VTA in mediating anxiety-like behaviors.

多巴胺 (DA) 作为控制情绪的关键调节剂，DA 信号的功能障碍与某些精神疾病（包括焦虑症）的病理生理学有关。腹侧被盖区 (VTA) 是产生 DA 的神经元的主要区域之一。中脑边缘大脑区域的 VTA DAergic 投射在调节焦虑样行为中起着至关重要的作用，然而，VTA 内 DA 信号在调节情绪中的功能仍不清楚。在这里，我们观察到 VTA D1 受体的药理学激活/抑制会减轻/加重小鼠焦虑样行为，并且 VTA D1 受体表达的敲低也会产生焦虑作用。通过荧光原位杂交和电生理记录，我们发现 D1 受体在 VTA 神经元中有功能性表达。沉默/激活 VTA D1 神经元双向调节小鼠焦虑样行为。此外，敲低 VTA DA 和谷氨酸神经元中的 D1 受体会提升焦虑样状态，但在 GABA 神经元中具有相反的效果。此外，我们确定从 VTA D1 神经元到侧隔的谷氨酸能投射主要负责通过激活 VTA D1 神经元诱导的抗焦虑作用。因此，我们的研究不仅描述了 VTA 神经元中 D1 受体的功能表达，还揭示了 VTA 中 DA 信号在介导焦虑样行为中的关键作用。我们确定从 VTA D1 神经元到侧隔的谷氨酸能投射主要负责通过激活 VTA D1 神经元诱导的抗焦虑作用。因此，我们的研究不仅描述了 VTA 神经元中 D1 受体的功能表达，还揭示了 VTA 中 DA 信号在介导焦虑样行为中的关键作用。我们确定从 VTA D1 神经元到侧隔的谷氨酸能投射主要负责通过激活 VTA D1 神经元诱导的抗焦虑作用。因此，我们的研究不仅描述了 VTA 神经元中 D1 受体的功能表达，还揭示了 VTA 中 DA 信号在介导焦虑样行为中的关键作用。