Progesterone receptor (PR) is expressed in Cajal-Retzius (CR) cells of the dentate gyrus (DG) molecular layer during the postnatal period (P1–28), a critical stage of development for the dentate gyrus and its circuitry. CR cells secrete the glycoprotein, reelin, which is required for typical development of the DG and its connections, particularly afferent input from the perforant path. This pathway regulates the processing of sensory information arriving from entorhinal cortex and integrates this information to form episodic memories. To assess the potential role of PR activity on the development of these connections and associated behavior, rats were treated daily from P1 to 7 with the PR antagonist, RU486. RU486 treatment increased the number of reelin-ir cells, suggesting an accumulation of reelin, and implicating PR in the regulation of a principle developmental function of CR cells. RU486 also altered the synaptic bouton marker, synaptophysin-ir, in a sex-specific manner, suggesting a role for PR activity in the development of perforant path innervation of the molecular layer (MOL). Finally, both control and RU486 treated rats spent significantly more time with a temporally distant object in the Relative Recency task, suggesting an intact associative memory for object identity and temporal order in both groups. In contrast, the same RU486 treated rats were impaired in an episodic-like memory task compared to controls, failing to integrate object identity (‘what’), time (‘when’), and object position (‘where’). These findings reveal a novel role for PR in regulating CR cell function within the MOL, thereby altering development of DG connectivity and behavioral function.

在产后阶段（P1-28），齿状回及其电路的发育的关键阶段，孕酮受体（PR）在齿状回（DG）分子层的Cajal-Retzius（CR）细胞中表达。CR细胞分泌糖蛋白reelin，这是DG及其连接的典型发育所必需的，尤其是穿孔路径的传入输入。该途径调节来自内嗅皮层的感觉信息的处理，并整合这些信息以形成情节记忆。为了评估PR活动在这些连接和相关行为发展中的潜在作用，每天用PR拮抗剂RU486从P1到7对大鼠进行治疗。RU486处理增加了reelin-ir细胞的数量，表明reelin的积累，并暗示PR参与CR细胞的主要发育功能的调节。RU486还以性别特异性方式改变了突触后的突触标记物synaptophysin-ir，表明PR活性在分子层（MOL）穿孔路径神经支配的发展中发挥了作用。最后，对照和RU486处理的大鼠在“相对新近性”任务中与时间上遥远的对象在一起花费的时间明显更多，这表明两组中对象身份和时间顺序的完整联想记忆。相反，与对照组相比，相同的RU486处理的大鼠在发作式记忆任务中受损，未能整合对象身份（“ what”），时间（“ when”）和对象位置（“ where”）。这些发现揭示了PR在调节MOL中CR细胞功能方面的新作用，