Prefrontal cortex (PFC) maturation during adolescence is characterized by structural and functional changes, which involve the remodeling of GABA and glutamatergic synapses, as well as changes in the endocannabinoid system. Yet, the way PFC endocannabinoid signaling interacts with local GABA and glutamatergic function to impact its processing of afferent transmission during the adolescent transition to adulthood remains unknown. Here we combined PFC local field potential recordings with local manipulations of 2-AG and anandamide levels to assess how PFC endocannabinoid signaling is recruited to modulate ventral hippocampal and basolateral amygdalar inputs in vivo in adolescent and adult male rats. We found that the PFC endocannabinoid signaling does not fully emerge until late-adolescence/young adulthood. Once present, both 2-AG and anandamide can be recruited in the PFC to limit the impact of hippocampal drive through a CB1R-mediated mechanism whereas basolateral amygdalar inputs are only inhibited by 2-AG. Similarly, the behavioral effects of increasing 2-AG and anandamide in the PFC do not emerge until late-adolescence/young adulthood. Using a trace fear conditioning paradigm, we found that elevating PFC 2-AG levels preferentially reduced freezing behavior during acquisition without affecting its extinction. In contrast, increasing anandamide levels in the PFC selectively disrupted the extinction of trace fear memory without affecting its acquisition. Collectively, these results indicate a protracted recruitment of PFC endocannabinoid signaling, which becomes online in late adolescence/young adulthood as revealed by its impact on hippocampal and amygdalar-evoked local field potential responses and trace fear memory behavior.

青春期前额皮质 (PFC) 成熟的特点是结构和功能变化，其中涉及 GABA 和谷氨酸突触的重塑，以及内源性大麻素系统的变化。然而，PFC 内源性大麻素信号传导与局部 GABA 和谷氨酸能功能相互作用以影响其在青少年向成年过渡期间传入传输的处理的方式仍然未知。在这里，我们将 PFC 局部场电位记录与 2-AG 和 anandamide 水平的局部操作相结合，以评估如何招募 PFC 内源性大麻素信号来调节青少年和成年雄性大鼠体内的腹侧海马和基底外侧杏仁核输入。我们发现 PFC 内源性大麻素信号传导直到青春期晚期/成年早期才完全出现。一旦存在，2-AG 和 anandamide 都可以在 PFC 中募集，通过 CB1R 介导的机制限制海马驱动的影响，而基底外侧杏仁核输入仅被 2-AG 抑制。同样，增加 PFC 中 2-AG 和 anandamide 的行为影响直到青春期后期/成年早期才会显现。使用微量恐惧调节范式，我们发现升高 PFC 2-AG 水平优先减少获得过程中的冻结行为，而不影响其消退。相比之下，增加前额皮质中的大麻素水平选择性地破坏微量恐惧记忆的消退，而不影响其获得。总的来说，这些结果表明 PFC 内源性大麻素信号传导的长期募集，在青春期后期/青年时期变得在线，正如它对海马和杏仁核诱发的局部场电位反应和追踪恐惧记忆行为的影响所揭示的那样。