Evidence for the persistence of contextual fear memories following immediate extinction

Evidence for the persistence of contextual fear memories following immediate extinction
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DOI:
10.1111/j.1460-9568.2010.07161.x
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发表时间:
2010-04-01
影响因子:
3.4
通讯作者:
Nader, Karim
Nader, Karim
中科院分区:
医学3区
文献类型:
--
作者:
Archbold, Georgina E. B.;Bouton, Mark E.;Nader, Karim

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证据表明,消亡是一种对巴甫洛夫信号的习得反应的抑制,这种反应是在条件作用后单独暴露于信号而产生的,是新的抑制性学习的结果。然而,有人提出,条件反射后立即出现的消退反映了记忆的“擦除”。利用语境恐惧条件作用,我们进一步研究了灭绝的本质,使用了一种新的行为范式,探索记忆的缺失或存在。大鼠接受三种不同电击强度(0.8、1.2或1.6 mA)中的一种,然后立即(15分钟)或延迟(24小时)消退。当在灭绝后24小时进行测试时,立即消失组和延迟消失组的自发恢复大致相同。为了进一步测试原始记忆痕迹的状态,我们利用了这样的效果,即只有第一次,而不是第二次,学习背景恐惧需要背侧海马区的N-甲基-D-天冬氨酸受体(NMDAR)[M.J.Sanders和M.S.Fanselow(2003)学习和记忆的神经生物学80,123-129]。在这里,我们使用第二次学习的特性来确定对立即消除的恐惧的记忆是否也会持续下去。在新的第二情境下进行训练之前,大鼠接受了双侧NMDAR拮抗剂DL-2-氨基-5-膦戊酸注入背侧海马区。NMDAR受体阻滞剂对二次学习记忆无影响,提示已熄灭的记忆不是被擦除,而是被抑制。总体而言,这些结果几乎没有证据表明,条件反射后立即进行的灭绝会破坏或抹去最初的记忆痕迹。
Evidence suggests that extinction, the suppression of a learned response to a Pavlovian signal that is produced by exposure to the signal alone after conditioning, is a consequence of new inhibitory learning. However, it has been proposed that extinction given immediately after conditioning reflects memory 'erasure'. Using contextual fear conditioning, we examine the nature of extinction further using a novel behavioral paradigm that probes for the absence or presence of a memory. Rats received a context paired with one of three different shock intensities (0.8, 1.2 or 1.6 mA) and then received extinction either immediately (15 min) or after a delay (24 h). Spontaneous recovery was roughly equivalent in the immediate and delayed extinction groups when they were tested at 24 h after extinction. To further test the status of the original memory trace, we exploited the effect that only the first, but not second, learning of contextual fear requires N-methyl-D-aspartate receptors (NMDArs) in the dorsal hippocampus [M.J. Sanders & M.S. Fanselow (2003) Neurobiology of Learning and Memory80,123-129]. Here we use this property of second learning to determine if memory of an immediately extinguished fear also persists. Rats received bilateral infusions of the NMDAr antagonist DL-2-amino-5-phosphonopentanoic acid into the dorsal hippocampus prior to training in a novel second context. Memory for the second learning is not affected by NMDAr blockade in either group, suggesting that the extinguished memory is not erased but inhibited. Overall, the results provide little evidence that extinction conducted immediately after conditioning destroys or erases the original memory trace.