BACKGROUND Dopamine (DA) is hypothesized to modulate anxiety-like behavior, although the precise role of DA in anxiety behaviors and the complete anxiety network in the brain have yet to be elucidated. Recent data indicate that dopaminergic projections from the ventral tegmental area (VTA) innervate the interpeduncular nucleus (IPN), but how the IPN responds to DA and what role this circuit plays in anxiety-like behavior are unknown. METHODS We expressed a genetically encoded G protein-coupled receptor activation-based DA sensor in mouse midbrain to detect DA in IPN slices using fluorescence imaging combined with pharmacology. Next, we selectively inhibited or activated VTA→IPN DAergic inputs via optogenetics during anxiety-like behavior. We used a biophysical approach to characterize DA effects on neural IPN circuits. Site-directed pharmacology was used to test if DA receptors in the IPN can regulate anxiety-like behavior. RESULTS DA was detected in mouse IPN slices. Silencing/activating VTA→IPN DAergic inputs oppositely modulated anxiety-like behavior. Two neuronal populations in the ventral IPN (vIPN) responded to DA via D1 receptors (D1Rs). vIPN neurons were controlled by a small population of D1R neurons in the caudal IPN that directly respond to VTA DAergic terminal stimulation and innervate the vIPN. IPN infusion of a D1R agonist and antagonist bidirectionally controlled anxiety-like behavior. CONCLUSIONS VTA DA engages D1R-expressing neurons in the caudal IPN that innervate vIPN, thereby amplifying the VTA DA signal to modulate anxiety-like behavior. These data identify a DAergic circuit that mediates anxiety-like behavior through unique IPN microcircuitry.

中文翻译：

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中脑多巴胺通过参与独特的脚间核微电路来控制焦虑样行为

背景 多巴胺 (DA) 被假设为调节焦虑样行为，尽管 DA 在焦虑行为中的确切作用和大脑中完整的焦虑网络尚未阐明。最近的数据表明，来自腹侧被盖区 (VTA) 的多巴胺能投射支配着脚间核 (IPN)，但 IPN 如何响应 DA 以及该回路在焦虑样行为中起什么作用尚不清楚。方法我们在小鼠中脑中表达了一种基于基因编码的 G 蛋白偶联受体激活的 DA 传感器，以使用荧光成像结合药理学来检测 IPN 切片中的 DA。接下来，我们在焦虑样行为期间通过光遗传学选择性地抑制或激活 VTA→IPN DAergic 输入。我们使用生物物理方法来表征 DA 对神经 IPN 电路的影响。定点药理学用于测试 IPN 中的 DA 受体是否可以调节焦虑样行为。结果 在小鼠 IPN 切片中检测到 DA。沉默/激活 VTA→IPN DAergic 输入相反地调节焦虑样行为。腹侧 IPN (vIPN) 中的两个神经元群通过 D1 受体 (D1R) 对 DA 做出反应。vIPN 神经元由尾端 IPN 中的一小群 D1R 神经元控制，这些神经元直接响应 VTA DAergic 终端刺激并支配 vIPN。IPN 输注 D1R 激动剂和拮抗剂双向控制焦虑样行为。结论 VTA DA 使尾端 IPN 中表达 D1R 的神经元参与支配 vIPN，从而放大 VTA DA 信号以调节焦虑样行为。