Bisby Madelyne A, Baker Kathryn D, Richardson Rick
School of Psychology, UNSW Sydney, New South Wales, 2052, Australia.
Learn Mem. 2018 Mar 15;25(4):158-164. doi: 10.1101/lm.047209.117. Print 2018 Apr.
NMDA receptors (NMDARs) are considered critical for the consolidation of extinction but recent work challenges this assumption. Namely, NMDARs are not required for extinction retention in infant rats as well as when extinction training occurs for a second time (i.e., reextinction) in adult rats. In this study, a possible third instance of NMDAR-independent extinction was tested. Although adolescents typically exhibit impaired extinction retention, rats that are conditioned as juveniles and then given extinction training as adolescents (JuvCond-AdolesExt) have good extinction retention. Unexpectedly, this good extinction retention is not associated with an up-regulation of a synaptic plasticity marker in the medial prefrontal cortex, a region implicated in extinction consolidation. In the current study, rats received either the noncompetitive NMDAR antagonist MK801 (0.1 mg/kg, s.c.) or saline before extinction training. In several experiments, rats conditioned and extinguished as juveniles, adolescents, or adults exhibited impaired extinction retention after MK801 compared to saline, but this effect was not observed in JuvCond-AdolesExt rats. Further experiments ruled out several alternative explanations for why NMDAR antagonism did not affect extinction retention in adolescents extinguishing fear learned as a juvenile. These results illustrate yet another circumstance in which NMDARs are not required for successful extinction retention and highlight the complexity of fear inhibition across development.
N-甲基-D-天冬氨酸受体（NMDARs）被认为对消退记忆的巩固至关重要，但最近的研究对这一假设提出了挑战。具体而言，在幼鼠中，以及成年大鼠再次进行消退训练（即重新消退）时，消退记忆的保持并不需要NMDARs。在本研究中，测试了NMDARs非依赖性消退的第三种可能情况。尽管青少年通常表现出消退记忆保持受损，但幼年时接受条件反射训练、青少年时接受消退训练的大鼠（幼年条件反射-青少年消退）具有良好的消退记忆保持能力。出乎意料的是，这种良好的消退记忆保持与内侧前额叶皮质（一个与消退巩固有关的区域）中突触可塑性标记物的上调无关。在本研究中，大鼠在消退训练前接受非竞争性NMDAR拮抗剂MK801（0.1mg/kg，皮下注射）或生理盐水。在几个实验中，幼年、青少年或成年时接受条件反射训练并进行消退训练的大鼠，与生理盐水组相比，在注射MK801后消退记忆保持受损，但在幼年条件反射-青少年消退的大鼠中未观察到这种效应。进一步的实验排除了NMDAR拮抗作用不影响青少年消退幼年习得恐惧的消退记忆保持的几种其他解释。这些结果说明了另一种成功保持消退记忆不需要NMDARs的情况，并突出了整个发育过程中恐惧抑制的复杂性。
