Dopaminergic neurotransmission is considered to play an important role not only in reward-based learning, but also in aversive learning. Here, we investigated the role of dopaminergic neurotransmission via dopamine D1 receptors (D1Rs) in aversive memory formation in a passive avoidance test using D1R knockdown (KD) mice, in which the expression of D1Rs can conditionally and reversibly be controlled by doxycycline (Dox) treatment. We also performed whole-brain imaging after aversive footshock stimulation in activity-regulated cytoskeleton protein (Arc)-dVenus D1RKD mice, which were crossbred from Arc-dVenus transgenic mice and D1RKD mice, to examine the distribution of Arc-controlled dVenus expression in the hippocampus and cerebral cortex during aversive memory formation. Knockdown of D1R expression following Dox treatment resulted in impaired performance in the passive avoidance test and was associated with a decrease in dVenus expression in the cerebral cortex (visual, somatosensory, and motor cortices), but not the hippocampus, compared with control mice without Dox treatment. These findings indicate that D1R-mediated dopaminergic transmission is critical for aversive memory formation, specifically by influencing Arc expression in the cerebral cortex.

中文翻译：

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大脑皮层中的厌恶记忆形成和弧激活需要通过多巴胺 D1 受体进行神经传递

多巴胺能神经传递被认为不仅在基于奖励的学习中发挥重要作用，而且在厌恶学习中也发挥着重要作用。在这里，我们在使用 D1R 敲低 (KD) 小鼠的被动回避测试中研究了通过多巴胺 D1 受体 (D1Rs) 进行的多巴胺能神经传递在厌恶记忆形成中的作用，其中 D1Rs 的表达可以由强力霉素 (Dox) 有条件地和可逆地控制治疗。我们还在活动调节的细胞骨架蛋白 (Arc)-dVenus D1RKD 小鼠（由 Arc-dVenus 转基因小鼠和 D1RKD 小鼠杂交而成）进行厌恶足电击刺激后进行全脑成像，以检查 Arc 控制的 dVenus 表达在厌恶记忆形成过程中的海马体和大脑皮层。与没有 Dox 的对照小鼠相比，Dox 治疗后 D1R 表达的敲低导致被动回避测试中的表现受损，并且与大脑皮层（视觉、躯体感觉和运动皮层）中的 dVenus 表达降低有关，但与海马体无关治疗。这些发现表明，D1R 介导的多巴胺能传递对于厌恶记忆的形成至关重要，特别是通过影响大脑皮层中的 Arc 表达。