School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.
School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China.
Neurobiol Learn Mem. 2018 Jul;152:1-9. doi: 10.1016/j.nlm.2018.04.011. Epub 2018 Apr 20.
Impairment in fear extinction is widely viewed as a major contributor to, or even an underlying mechanism of, the pathogenesis of anxiety disorders and PTSD. Children with traumatic experience have a higher risk for developing anxiety disorders and PTSD in the adult. Little is known about the nature of fear memory extinction and its underlying mechanism during this period. Here we showed that while renewal of fear memory is context-specific in adult mice, it is absent in infant mice (P17). Using local injection of GABAa receptor antagonist picrotoxin, we found that there is no functional connectivity between infralimbic prefrontal cortex and hippocampus in P17 mice, while prefrontal cortex projection to amygdala is functioning. Hence, the lack of fear renewal is likely caused by the lack of connections between hippocampus and prefrontal cortex which are known to be involved in the regulation of extinction memory.
恐惧消退受损被广泛认为是焦虑障碍和创伤后应激障碍发病机制的主要因素，甚至是其潜在机制。有创伤经历的儿童在成年后患焦虑障碍和创伤后应激障碍的风险更高。在此期间，关于恐惧记忆消退的本质及其潜在机制知之甚少。在这里，我们表明，虽然成年小鼠的恐惧记忆再现具有特定于情境的特征，但在 P17 幼鼠中则不存在（P17）。使用 GABAa 受体拮抗剂荷包牡丹碱局部注射，我们发现 P17 小鼠的下丘脑边缘前脑皮质和海马之间没有功能连接，而前额叶皮质投射到杏仁核的功能正常。因此，恐惧再现的缺乏可能是由于海马和前额叶皮质之间的连接缺失所致，已知这些连接参与了消退记忆的调节。
