Memory Center, Brain Institute, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6690 - 2nd floor, 90610-000 Porto Alegre, RS, Brazil.
Memory Center, Brain Institute, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6690 - 2nd floor, 90610-000 Porto Alegre, RS, Brazil.
Behav Brain Res. 2022 Jul 26;430:113948. doi: 10.1016/j.bbr.2022.113948. Epub 2022 May 27.
Wnt proteins activate different signaling pathways, such as the canonical Wnt/β-catenin signaling pathway and non-canonical β-catenin-independent signaling pathway and have been related to several functions in central nervous system, including learning and memory. However, whether these signaling pathways are required in the medial prefrontal cortex (mPFC) for fear memory acquisition, consolidation and retrieval remains unclear. To address this question, we submitted male rats to a contextual fear conditioning (CFC) paradigm, and administered canonical Wnt/β-catenin and non-canonical Wnt/Ca signaling pathways inhibitors, DKK1 and SFRP1, respectively, into the prelimbic (PrL) subdivision of the mPFC at different moments and evaluated short-term and long-term memory acquisition, consolidation and retrieval. We found that blocking canonical Wnt/β-catenin and non-canonical Wnt/Ca signaling pathways 15 min before or immediately after CFC training had no effect on STM and LTM of CFC, while their blockade 15 min before the retention test prevented the retrieval of STM and LTM of CFC. These results highlight the importance of the mPFC in fear memory retrieval demonstrating that both canonical Wnt/β-catenin and non-canonical Wnt/Ca signaling pathways participate in this process. To understand how brain systems act on fear memories could provide a new target for the treatment of fear related disorders such as post-traumatic stress disorder and other anxiety disorders.
Wnt 蛋白激活不同的信号通路，如经典的 Wnt/β-连环蛋白信号通路和非经典的β-连环蛋白非依赖性信号通路，并与中枢神经系统的几种功能有关，包括学习和记忆。然而，这些信号通路是否需要在中前额叶皮层（mPFC）中参与恐惧记忆的获得、巩固和检索尚不清楚。为了解决这个问题，我们让雄性大鼠接受情境性恐惧条件反射（CFC）范式，并在不同时间将经典 Wnt/β-连环蛋白和非经典 Wnt/Ca 信号通路抑制剂 DKK1 和 SFRP1 分别注入 mPFC 的额前皮质（PrL）亚区，并评估短期和长期记忆的获得、巩固和检索。我们发现，在 CFC 训练前 15 分钟或立即阻断经典 Wnt/β-连环蛋白和非经典 Wnt/Ca 信号通路，对 CFC 的 STM 和 LTM 没有影响，而在保留测试前 15 分钟阻断它们，阻止了 CFC 的 STM 和 LTM 的检索。这些结果强调了 mPFC 在恐惧记忆检索中的重要性，表明经典 Wnt/β-连环蛋白和非经典 Wnt/Ca 信号通路都参与了这个过程。了解大脑系统如何对恐惧记忆起作用，可能为治疗与创伤后应激障碍和其他焦虑障碍等恐惧相关障碍提供新的靶点。
