Mississauga Department of Psychology, University of Toronto, Mississauga, Ontario, Canada.
Center for Studies in Behavioural Neurobiology, Department of Psychology, Concordia University, Montreal, Quebec, Canada.
PLoS One. 2023 Jun 22;18(6):e0287193. doi: 10.1371/journal.pone.0287193. eCollection 2023.
Research on memory reconsolidation has relied heavily on the use of Pavlovian auditory cued-fear conditioning. Here, an auditory cue (CS) is paired with a footshock (US) and the CS is later able to evoke a freezing response when presented alone. Some treatments, when administered to conditioned subjects immediately following a CS-alone (memory reactivation) trial, can attenuate the freezing they display on subsequent CS-alone (test) trials, in the absence of the treatment. This reduction in conditioned freezing is usually taken as evidence that the treatment disrupts post-reactivation reconsolidation of the memory trace representing the pairing of CS and US. We suggest an alternative interpretation that may account, either in whole or in part, for the attenuated freezing. The standard reconsolidation protocol (SRP) for auditory fear-conditioning has a design feature that results in second-order conditioning of fear to the test context, as this context is paired with the fear-evoking CS on the reactivation trial. Since freezing during the CS on the test will reflect the compound influence of contextual-fear and cued-fear, a post-reactivation treatment might attenuate freezing on the test by disrupting consolidation of second-order contextual-fear conditioning, even if it has little or no effect on the stability of the original cued-fear memory. This experiment confirmed that rats tested according to the SRP, in which the reactivation and test trials occur in the same context, freeze more on the test trial than rats that receive the reactivation and test trials in different contexts. This confound could lead to false-positive evidence of disrupted reconsolidation if it is not avoided or minimized, which can be accomplished with a modified protocol.
记忆再巩固的研究主要依赖于使用条件性听觉恐惧条件反射。在这里，一个听觉提示（CS）与电击（US）配对，并且当单独呈现 CS 时，CS 后来能够引起冻结反应。一些治疗方法，在条件性受试者在 CS 单独（记忆再激活）试验后立即给予，当在没有治疗的情况下，可减弱它们在随后的 CS 单独（测试）试验中显示的冻结。这种条件性冻结的减少通常被视为治疗方法破坏了代表 CS 和 US 配对的记忆痕迹的再激活后再巩固的证据。我们提出了一种替代解释，该解释可能全部或部分解释了减弱的冻结。听觉恐惧条件反射的标准再巩固方案（SRP）具有一种设计特征，导致对测试上下文的二级条件恐惧，因为该上下文在再激活试验中与引起恐惧的 CS 配对。由于在测试中的 CS 期间的冻结将反映上下文恐惧和提示恐惧的复合影响，因此再激活后治疗可能通过破坏二级上下文恐惧条件的巩固来减弱测试中的冻结，即使它对原始提示恐惧记忆的稳定性几乎没有影响或没有影响。该实验证实，根据 SRP 进行测试的大鼠，在再激活和测试试验发生在同一环境中，比接受再激活和测试试验在不同环境中的大鼠在测试试验中冻结更多。如果不避免或最小化这种混淆，它可能会导致再巩固被破坏的假阳性证据，这可以通过修改协议来实现。
