A critical feature of episodic memory formation is to associate temporally segregated events as an episode, called temporal association learning. The medial entorhinal cortical-hippocampal (EC-HPC) networks is essential for temporal association learning. We have previously demonstrated that pyramidal cells in the medial EC (MEC) layer III project to the hippocampal CA1 pyramidal cells and are necessary for trace fear conditioning (TFC), which is an associative learning between tone and aversive shock with the temporal gap. On the other hand, Island cells in MECII, project to GABAergic neurons in hippocampal CA1, suppress the MECIII input into the CA1 pyramidal cells through the feed-forward inhibition, and inhibit TFC. However, it remains unknown about how Island cells activity is regulated during TFC. In this study, we report that dopamine D1 receptor is preferentially expressed in Island cells in the MEC. Optogenetic activation of dopamine D1 receptors in Island cells facilitate the Island cell activity and inhibited hippocampal CA1 pyramidal cell activity during TFC. The optogenetic activation caused the impairment of TFC memory recall without affecting contextual fear memory recall. These results suggest that dopamine D1 receptor in Island cells have a crucial role for the regulation of temporal association learning.

中文翻译：

---

内侧内嗅皮层岛细胞多巴胺 D1 受体的光遗传学激活抑制时间关联学习

情景记忆形成的一个关键特征是将暂时分离的事件关联为一个情景，称为时间关联学习。内侧内嗅皮层海马 (EC-HPC) 网络对于时间关联学习至关重要。我们之前已经证明，内侧 EC (MEC) 第三层中的锥体细胞投射到海马 CA1 锥体细胞，并且对于痕量恐惧调节 (TFC) 是必需的，TFC 是音调和厌恶性休克与时间间隙之间的关联学习。另一方面，MECII中的岛细胞投射到海马CA1中的GABA能神经元，通过前馈抑制抑制MECIII输入到CA1锥体细胞中，并抑制TFC。然而，关于 TFC 期间岛细胞活性如何受到调节仍不清楚。在这项研究中，我们报告多巴胺 D1 受体优先在 MEC 的岛细胞中表达。在 TFC 期间，岛细胞中多巴胺 D1 受体的光遗传学激活促进岛细胞活性并抑制海马 CA1 锥体细胞活性。光遗传学激活导致 TFC 记忆回忆受损，但不影响情境恐惧记忆回忆。这些结果表明岛细胞中的多巴胺 D1 受体对于时间关联学习的调节具有至关重要的作用。