Levitan David, Gal-Ben-Ari Shunit, Heise Christopher, Rosenberg Tali, Elkobi Alina, Inberg Sharon, Sala Carlo, Rosenblum Kobi
Sagol Department of Neurobiology, Center for Gene Manipulation in the Brain, University of Haifa, Mt Carmel, Haifa, Israel.
Consiglio Nazionale delle Ricerche Neuroscience Institute and Department of Biotechnology and Translational Medicine, University of Milano, Milan, Italy.
NPJ Sci Learn. 2016;1:16001. doi: 10.1038/npjscilearn.2016.1. Epub 2016 May 11.
The current dogma suggests that the formation of long-term memory (LTM) is dependent on protein synthesis but persistence of the memory trace is not. However, many of the studies examining the effect of protein synthesis inhibitors (PSIs) on LTM persistence were performed in the hippocampus, which is known to have a time-dependent role in memory storage, rather than the cortex, which is considered to be the main structure to store long-term memories. Here we studied the effect of PSIs on LTM formation and persistence in male Wistar Hola ( ≥ 5) rats by infusing the protein synthesis inhibitor, anisomycin (100 μg, 1 μl), into the gustatory cortex (GC) during LTM formation and persistence in conditioned taste aversion (CTA). We found that local anisomycin infusion to the GC before memory acquisition impaired LTM formation ( = 8.9E - 5), but had no effect on LTM persistence when infused 3 days post acquisition ( = 0.94). However, when we extended the time interval between treatment with anisomycin and testing from 3 days to 14 days, LTM persistence was enhanced ( = 0.01). The enhancement was on the background of stable and non-declining memory, and was not recapitulated by another amnesic agent, APV (10 μg, 1 μl), an -methyl-d-aspartate receptor antagonist ( = 0.54). In conclusion, CTA LTM remains sensitive to the action of PSIs in the GC even 3 days following memory acquisition. This sensitivity is differentially expressed between the formation and persistence of LTM, suggesting that increased cortical protein synthesis promotes LTM formation, whereas decreased protein synthesis promotes LTM persistence.
目前的主流观点认为,长期记忆(LTM)的形成依赖于蛋白质合成,但记忆痕迹的持续则并非如此。然而,许多研究蛋白质合成抑制剂(PSIs)对LTM持续影响的实验是在海马体中进行的,海马体在记忆存储中具有时间依赖性作用,而非在被认为是存储长期记忆的主要结构的皮层中进行。在此,我们通过在条件性味觉厌恶(CTA)的LTM形成和持续过程中,向味觉皮层(GC)注入蛋白质合成抑制剂茴香霉素(100μg,1μl),研究了PSIs对雄性Wistar Hola(≥5)大鼠LTM形成和持续的影响。我们发现,在记忆获取前向GC局部注入茴香霉素会损害LTM的形成(P = 8.9E - 5),但在获取后3天注入时对LTM的持续没有影响(P = 0.94)。然而,当我们将茴香霉素处理与测试之间的时间间隔从3天延长至14天时,LTM的持续得到了增强(P = 0.01)。这种增强是在记忆稳定且不衰退的背景下发生的,并且另一种失忆剂——α-甲基-D-天冬氨酸受体拮抗剂APV(10μg,1μl)并未重现这种增强效果(P = 0.54)。总之,即使在记忆获取后3天,CTA的LTM对GC中PSIs的作用仍保持敏感。这种敏感性在LTM的形成和持续过程中表现不同,表明皮层蛋白质合成增加促进LTM的形成,而蛋白质合成减少则促进LTM的持续。