Extinction trial spacing across days differentially impacts fear regulation in adult and adolescent male mice

Abstract

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.

Keywords: Adolescence; Consolidation; Fear extinction; Massed learning; Memory; Spaced learning.