Department of Psychiatry, Weill Cornell Medicine, New York, NY, United States.
Department of Psychiatry, Weill Cornell Medicine, New York, NY, United States; Department of Psychological and Brain Sciences, Boston University, Boston, MA, United States.
Neurobiol Learn Mem. 2021 Dec;186:107543. doi: 10.1016/j.nlm.2021.107543. Epub 2021 Nov 5.
Fear regulation changes as a function of age and adolescence is a key developmental period for the continued maturation of fear neural circuitry. A consistent finding in the literature is diminished extinction retention in adolescents. However, these studies often directly compare adolescents to adults using a single protocol and therefore provide little insight into learning parameters that improve adolescent fear regulation. Studies in adults highlight the benefits of spaced learning over massed learning. These findings have been extended to fear regulation, with adult rodents exhibiting improved extinction learning and retention when cues are distributed over days versus a single session. However, similar studies have not been performed in adolescents. Here, we systematically examine the impact of trial spacing across days on fear regulation. Adolescent or adult male mice were exposed to one of three extinction paradigms that presented the same number of trials but differed in the temporal distribution of trials across days (one day, two days, or four days). We found that introducing consolidation events into the protocol improves adult extinction learning and short-term extinction retention but these effects disappear after two weeks. For adolescents, all three protocols were comparably effective in reducing freezing across extinction training and improved retention at both short-term and long-term fear recall time points relative to extinction-naive mice. These findings suggest that extinction protocols that incorporate consolidation events are optimal for adults but additional booster training may be required for enduring efficacy. In contrast, protocols incorporating either massed or spaced presentations show immediate and enduring benefits for adolescents.
恐惧调节会随着年龄和青春期的变化而变化，青春期是恐惧神经回路持续成熟的关键发育阶段。文献中的一个一致发现是，青少年的消退保持能力下降。然而，这些研究通常直接将青少年与成年人进行比较，使用单一方案，因此几乎没有深入了解改善青少年恐惧调节的学习参数。成人研究强调了间隔学习优于集中学习的好处。这些发现已经扩展到恐惧调节中，成年啮齿动物在提示分布在几天而不是单个会话时表现出更好的消退学习和保留。然而，类似的研究尚未在青少年中进行。在这里，我们系统地检查了跨天试验间隔对恐惧调节的影响。青少年或成年雄性小鼠接受了三种消退范式中的一种，这些范式呈现了相同数量的试验，但在跨天的试验时间分布上有所不同（一天、两天或四天）。我们发现，在方案中引入巩固事件可改善成年消退学习和短期消退保持，但这些效果在两周后消失。对于青少年，所有三种方案在整个消退训练过程中都能有效地减少冻结，并在短期和长期恐惧回忆时间点相对于未经历消退的小鼠提高保留。这些发现表明，纳入巩固事件的消退方案对成年人是最佳的，但对于持久疗效，可能需要额外的强化训练。相比之下，包含集中或间隔呈现的方案对青少年具有即时和持久的益处。
