Department of Psychology, Stony Brook University, 100 Nicolls Rd., Stony Brook, NY, 11794, USA.
Psychopharmacology (Berl). 2019 Jul;236(7):2039-2048. doi: 10.1007/s00213-019-05195-2. Epub 2019 Feb 23.
Although most individuals will be exposed to trauma at some point, only a small portion of individuals develops posttraumatic stress disorder (PTSD), suggesting there are factors which render some individuals particularly susceptible to the development of this disorder. One cardinal feature of PTSD is the failure to extinguish fear responses to cues that once signaled danger. Rodent studies of fear learning and extinction have provided insight into the neural mechanisms underlying extinction; however, most of these studies have focused on mechanisms involved in typical responses and fewer have identified mechanisms that distinguish animals that extinguish well versus those that do not extinguish their fear responses. Investigation of individual differences in fear extinction might help us better understand the susceptibility to and development of PTSD.
In order to understand the neural mechanisms underlying such variation, we assessed phosphorylated mitogen-activated protein kinase (P-MAPK) levels in infralimbic cortex (IL), basolateral amygdala (BLA), and dorsal hippocampus in subsets of rats which exhibited good or poor recall of extinction.
We found a relationship between extinction recall and P-MAPK in the IL such that rats which had good extinction recall had higher levels of P-MAPK than those which had poor extinction recall. We also found that rats which had good extinction recall had higher levels of P-MAPK in the dorsal hippocampus than control rats.
Our findings suggest that individual differences in the recall of extinction learning can be explained by altered cell signaling in the IL.
尽管大多数人都会在某个时候接触到创伤,但只有一小部分人会发展出创伤后应激障碍(PTSD),这表明有些个体特别容易患上这种疾病,存在一定的因素。PTSD 的一个主要特征是,当曾经表示危险的线索再次出现时,无法消除对恐惧反应的抑制。关于恐惧学习和遗忘的啮齿动物研究为理解遗忘的神经机制提供了线索;然而,这些研究大多集中在典型反应所涉及的机制上,而较少关注能够区分能够很好地消除恐惧反应的动物和不能消除恐惧反应的动物的机制。对恐惧遗忘中的个体差异的研究可能有助于我们更好地理解易感性和 PTSD 的发展。
为了了解这种差异的神经机制基础,我们评估了在表现出良好或不良遗忘回忆的大鼠亚组中,边缘下皮层(IL)、基底外侧杏仁核(BLA)和背侧海马中的磷酸化丝裂原活化蛋白激酶(P-MAPK)水平。
我们发现遗忘回忆与 IL 中的 P-MAPK 之间存在关系,即具有良好遗忘回忆的大鼠比具有不良遗忘回忆的大鼠具有更高水平的 P-MAPK。我们还发现,具有良好遗忘回忆的大鼠的背侧海马中的 P-MAPK 水平高于对照大鼠。
我们的发现表明,遗忘学习回忆中的个体差异可以通过 IL 中的细胞信号转导改变来解释。