Jung Seung H, Meckes Jeanie K, Schipma Matthew J, Lim Patrick H, Jenz Sophia T, Przybyl Katherine, Wert Stephanie L, Kim Sarah, Luo Wendy, Gacek Stephanie A, Jankord Ryan, Hatcher-Solis Candice, Redei Eva E
Applied Neuroscience, 711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson Air Force Base, OH, USA.
Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Neuroscience. 2020 Sep 15;444:76-91. doi: 10.1016/j.neuroscience.2020.07.052. Epub 2020 Aug 5.
The role of stress in altering fear memory is not well understood. Since individual variations in stress reactivity exist, and stress alters fear memory, exposing individuals with differing stress-reactivity to repeated stress would affect their fear memory to various degrees. We explored this question using the average stress-reactive Fisher 344 (F344) rat strain and the Wistar-Kyoto (WKY) strain with its heightened stress-reactivity. Male F344 and WKY rats were exposed to the contextual fear conditioning (CFC) paradigm and then chronic restraint stress (CRS) or no stress (NS) was administered for two weeks before a second CFC. Both recent and reinstated fear memory were greater in F344s than WKYs, regardless of the stress status. In contrast, remote memory was attenuated only in F344s after CRS. In determining whether this strain-specific response to CRS was mirrored by transcriptomic changes in the blood, RNA sequencing was carried out. Overlapping differentially expressed genes (DEGs) between NS and CRS in the blood of F344 and WKY suggest a convergence of stress-related molecular mechanisms, independent of stress-reactivity. In contrast, DEGs unique to the F344 and the WKY stress responses are divergent in their functionality and networks, beyond that of strain differences in their non-stressed state. These results suggest that in some individuals chronic or repeated stress, different from the original fear memory-provoking stress, can attenuate prior fear memory. Furthermore, the novel blood DEGs can report on the general state of stress of the individual, or can be associated with individual variation in stress-responsiveness.
压力在改变恐惧记忆方面的作用尚未得到充分理解。由于存在压力反应性的个体差异，且压力会改变恐惧记忆，让具有不同压力反应性的个体反复暴露于压力之下会在不同程度上影响他们的恐惧记忆。我们使用平均压力反应性的费希尔344（F344）大鼠品系和压力反应性增强的Wistar-Kyoto（WKY）品系来探究这个问题。雄性F344和WKY大鼠接受情境恐惧条件反射（CFC）范式，然后在第二次CFC之前的两周给予慢性束缚应激（CRS）或无应激（NS）。无论应激状态如何，F344大鼠的近期恐惧记忆和恢复的恐惧记忆都比WKY大鼠更强。相比之下，CRS后只有F344大鼠的远期记忆减弱。在确定这种对CRS的品系特异性反应是否在血液转录组变化中得到体现时，我们进行了RNA测序。F344和WKY血液中NS与CRS之间重叠的差异表达基因（DEG）表明，与压力相关的分子机制存在趋同，与压力反应性无关。相比之下，F344和WKY应激反应特有的DEG在功能和网络方面存在差异，超出了它们非应激状态下的品系差异。这些结果表明，在一些个体中，与最初引发恐惧记忆的压力不同的慢性或反复压力会减弱先前的恐惧记忆。此外，新发现的血液DEG可以反映个体的一般压力状态，或者与个体在压力反应性方面的差异相关。
