Department of Psychology, University of Haifa, Haifa 3498838, Israel.
Sagol Department of Neurobiology, University of Haifa, Haifa 3498838, Israel.
Eur Neuropsychopharmacol. 2017 Sep;27(9):900-912. doi: 10.1016/j.euroneuro.2017.06.007. Epub 2017 Jun 22.
Studies about reconsolidation of conditioned fear memories have shown that pharmacological manipulation at memory reactivation can attenuate or enhance the subsequent expression of the conditioned fear response. Here we examined the effects of a single injection of the mTOR inhibitor rapamycin (Rap) into the infralimbic (IL) and prelimbic (PL) areas [which compose the ventromedial prefrontal cortex (PFC)] on reconsolidation and extinction of a traumatic fear memory. We found opposite effects of Rap infused into the PL and IL on reconsolidation and extinction: intra-PL Rap and systemic Rap impaired reconsolidation and facilitated extinction whereas intra-IL Rap enhanced reconsolidation and impaired extinction. These effects persisted at least 10 days after reactivation. Shock exposure induced anxiety-like behavior and impaired working memory and intra-IL and -PL Rap normalized these effects. Finally, when measured after fear retrieval, shocked rats exhibited reduced and increased phosphorylated p70s6K levels in the IL and basolateral amygdala, respectively. No effect on phosphorylated p70s6K levels was observed in the PL. The study points to the differential roles of the IL and PL in memory reconsolidation and extinction. Moreover, inhibiting mTOR via rapamycin following reactivation of a fear memory may be a novel approach in attenuating enhanced fear memories.
关于条件性恐惧记忆再巩固的研究表明,在记忆再激活时进行药理学处理可以减弱或增强条件性恐惧反应的后续表达。在这里,我们研究了单次注射雷帕霉素(mTOR 抑制剂)到侧前额叶皮层腹内侧(IL)和额前皮质(PL)区域[组成腹内侧前额叶皮层(PFC)]对创伤性恐惧记忆再巩固和消退的影响。我们发现,雷帕霉素注入 PL 和 IL 对再巩固和消退有相反的影响:PL 内雷帕霉素和全身雷帕霉素损害再巩固并促进消退,而 IL 内雷帕霉素增强再巩固并损害消退。这些影响至少在再激活后 10 天内持续存在。休克暴露引起焦虑样行为和工作记忆受损,而 IL 和 PL 内雷帕霉素使这些影响正常化。最后,在恐惧检索后测量时,受惊吓的大鼠在 IL 和杏仁核基底外侧分别表现出磷酸化 p70s6K 水平降低和增加。PL 中未观察到磷酸化 p70s6K 水平的变化。该研究指出了 IL 和 PL 在记忆再巩固和消退中的差异作用。此外,在恐惧记忆再激活后通过雷帕霉素抑制 mTOR 可能是减弱增强的恐惧记忆的一种新方法。