Department of Neurology, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Germany.
Department of Neurology, BG University Hospital Bergmannsheil, Ruhr-University Bochum, Germany.
Neurobiol Learn Mem. 2022 Oct;194:107672. doi: 10.1016/j.nlm.2022.107672. Epub 2022 Jul 30.
While the renewal effect of extinction is considered to be invoked by attention to context during the extinction phase, there is also evidence that processing during initial learning (acquisition) may be important for later renewal. A noradrenergic agonist and a dopaminergic antagonist, administered before acquisition, did not affect renewal, however, the effects of NMDAergic neurotransmission in this regard are as yet unknown. In a previous study, administration of a single dose of the NMDA agonist d-cycloserine (DCS) before extinction learning facilitated extinction in the context of acquisition (AAA), but had no effect upon renewal. In the present fMRI study, DCS was administered prior to the initial acquisition of a predictive learning task, in order to investigate whether NMDA receptor (NMDAR) stimulation at this timepoint will modulate overall learning as well as the level of renewal, while increasing activation in the extinction- and renewal-relevant brain regions of inferior frontal gyrus (iFG) and hippocampus (HC). DCS facilitated acquisition, as well as extinction learning in the context of acquisition (AAA), and raised the level of ABA renewal. While BOLD activation during acquisition did not differ between treatment groups, activation in bilateral iFG showed a double dissociation during processing of AAA extinction trials, with DCS-mediated higher activation in right iFG and deactivation in left iFG. In contrast, placebo showed higher activation in left iFG and deactivation in right iFG. During the test (recall) phase, left iFG and right anterior hippocampus activation was increased in DCS participants who showed renewal, with activation in this region correlating with the ABA renewal level. The results demonstrate that NMDA receptor stimulation can facilitate both initial learning and extinction of associations, and in this way has an impact upon the resultant level of renewal. In particular NMDAergic processing in iFG appears relevant for the facilitation of AAA extinction and ABA recall in the test phase.
虽然在灭绝阶段注意上下文被认为会引发灭绝的更新效应，但也有证据表明，初始学习（获得）期间的处理对于后期的更新可能很重要。在获得之前给予去甲肾上腺素能激动剂和多巴胺能拮抗剂不会影响更新，但是，关于这方面的 NMDA 能神经传递的作用尚不清楚。在以前的研究中，在灭绝学习之前给予单次剂量的 NMDA 激动剂 d-环丝氨酸（DCS）会促进获得背景下的灭绝（AAA），但对更新没有影响。在本 fMRI 研究中，在初始获得预测性学习任务之前给予 DCS，以研究 NMDA 受体（NMDAR）刺激在此时是否会调节整体学习以及更新水平，同时增加下额叶（iFG）和海马（HC）与灭绝和更新相关的大脑区域的激活。DCS 促进了获得以及获得背景下的灭绝学习（AAA），并提高了 ABA 更新的水平。虽然在治疗组之间获得期间的 BOLD 激活没有差异，但双侧 iFG 在处理 AAA 灭绝试验时表现出双重分离，DCS 介导的右侧 iFG 激活增加和左侧 iFG 去激活。相比之下，安慰剂显示左侧 iFG 激活增加和右侧 iFG 去激活。在测试（回忆）阶段，在表现出更新的 DCS 参与者中，左侧 iFG 和右侧前海马的激活增加，该区域的激活与 ABA 更新水平相关。结果表明，NMDA 受体刺激可以促进关联的初始学习和灭绝，并且以这种方式对更新的最终水平产生影响。特别是 iFG 中的 NMDA 能处理对于促进 AAA 灭绝和测试阶段的 ABA 回忆很重要。
