Ye Xiaojing, Kapeller-Libermann Dana, Travaglia Alessio, Inda M Carmen, Alberini Cristina M
Center for Neural Science, New York University, New York, New York, USA.
Nat Neurosci. 2017 Jan;20(1):52-61. doi: 10.1038/nn.4443. Epub 2016 Nov 21.
The ability to regulate the consolidation and strengthening of memories for threatening experiences is critical for mental health, and its dysregulation may lead to psychopathologies. Re-exposure to the context in which the threat was experienced can either increase or decrease fear response through distinct processes known, respectively, as reconsolidation or extinction. Using a context retrieval-dependent memory-enhancement model in rats, we report that memory strengthens through activation of direct projections from dorsal hippocampus to prelimbic (PL) cortex and activation of critical PL molecular mechanisms that are not required for extinction. Furthermore, while sustained PL brain-derived neurotrophic factor (BDNF) expression is required for memory consolidation, retrieval engages PL BDNF to regulate excitatory and inhibitory synaptic proteins neuroligin 1 and neuroligin 2, which promote memory strengthening while inhibiting extinction. Thus, context retrieval-mediated fear-memory enhancement results from a concerted action of mechanisms that strengthen memory through reconsolidation while suppressing extinction.
调节对威胁性经历的记忆巩固和强化的能力对心理健康至关重要，其调节异常可能导致精神病理学。再次暴露于经历威胁的情境中，可以通过分别称为重新巩固或消退的不同过程增加或减少恐惧反应。使用大鼠的情境检索依赖记忆增强模型，我们报告记忆通过激活从背侧海马到前边缘（PL）皮质的直接投射以及激活消退不需要的关键PL分子机制而得到加强。此外，虽然持续的PL脑源性神经营养因子（BDNF）表达是记忆巩固所必需的，但检索会促使PL BDNF调节兴奋性和抑制性突触蛋白神经连接蛋白1和神经连接蛋白2，它们在抑制消退的同时促进记忆强化。因此，情境检索介导的恐惧记忆增强是通过在抑制消退的同时通过重新巩固加强记忆的机制协同作用产生的。
