Safety learning during adolescence facilitates fear regulation in adult mice

Experiences during sensitive early life developmental periods such as adolescence have a profound influence on brain maturation and long-term affective behavior. While substantial work focuses on early life adversity, emerging evidence suggests that positive affective experiences can also shape traj...

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Main Author: Heidi C. Meyer
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Developmental Cognitive Neuroscience
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Online Access:http://www.sciencedirect.com/science/article/pii/S187892932500101X
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author Heidi C. Meyer
author_facet Heidi C. Meyer
author_sort Heidi C. Meyer
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description Experiences during sensitive early life developmental periods such as adolescence have a profound influence on brain maturation and long-term affective behavior. While substantial work focuses on early life adversity, emerging evidence suggests that positive affective experiences can also shape trajectories of neurobehavioral development. This study examined how experience with fear conditioning or discriminative conditioning (i.e., safety learning) during either adolescence or adulthood in male and female mice influenced fear behavior and engagement with an anxiogenic environment one month later, when adolescents had aged to adulthood. Prior conditioning (both fear and safety training) at either age, regardless of valence, promoted later fear generalization to a novel cue. In contrast, safety learning during adolescence conferred enduring benefits, leading to reduced fear expression and enhanced extinction memory in adulthood, whereas similar training in adulthood offered limited protective effects. Behavior in the elevated plus maze revealed increased movement in all previously conditioned animals (both Fear-trained and Safety-trained groups), with safety learning decreasing initial freezing in the maze and accelerating initial re-location from the placement arm. Sex differences in this study were modest, showing limited interaction with age and minimal impact on training-related outcomes across experimental phases, suggesting that the effects of conditioning on later affective regulation are robust and broadly conserved across sexes. Overall, these findings highlight adolescence as a sensitive period during which safety learning can shape affective regulation and potentially buffer against later life pathological fear responding. This work offers insight into developmental mechanisms that may inform early interventions for psychiatric conditions like anxiety.
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spelling doaj-art-9cac09f23ab84e0f886dfa82cee03a9e2025-08-25T04:14:12ZengElsevierDevelopmental Cognitive Neuroscience1878-92932025-10-017510160610.1016/j.dcn.2025.101606Safety learning during adolescence facilitates fear regulation in adult miceHeidi C. Meyer0Department of Psychiatry, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA; Department of Psychological and Brain Sciences, Boston University, 610 Commonwealth Ave, Boston, MA 02215, USA; Center for Systems Neuroscience, Boston University, 610 Commonwealth Ave, Boston, MA 02215, USA.; Corresponding author at: Department of Psychiatry, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA.Experiences during sensitive early life developmental periods such as adolescence have a profound influence on brain maturation and long-term affective behavior. While substantial work focuses on early life adversity, emerging evidence suggests that positive affective experiences can also shape trajectories of neurobehavioral development. This study examined how experience with fear conditioning or discriminative conditioning (i.e., safety learning) during either adolescence or adulthood in male and female mice influenced fear behavior and engagement with an anxiogenic environment one month later, when adolescents had aged to adulthood. Prior conditioning (both fear and safety training) at either age, regardless of valence, promoted later fear generalization to a novel cue. In contrast, safety learning during adolescence conferred enduring benefits, leading to reduced fear expression and enhanced extinction memory in adulthood, whereas similar training in adulthood offered limited protective effects. Behavior in the elevated plus maze revealed increased movement in all previously conditioned animals (both Fear-trained and Safety-trained groups), with safety learning decreasing initial freezing in the maze and accelerating initial re-location from the placement arm. Sex differences in this study were modest, showing limited interaction with age and minimal impact on training-related outcomes across experimental phases, suggesting that the effects of conditioning on later affective regulation are robust and broadly conserved across sexes. Overall, these findings highlight adolescence as a sensitive period during which safety learning can shape affective regulation and potentially buffer against later life pathological fear responding. This work offers insight into developmental mechanisms that may inform early interventions for psychiatric conditions like anxiety.http://www.sciencedirect.com/science/article/pii/S187892932500101XAdolescenceSafetyFearLearningEarly Life ExperienceAnxiety
spellingShingle Heidi C. Meyer
Safety learning during adolescence facilitates fear regulation in adult mice
Developmental Cognitive Neuroscience
Adolescence
Safety
Fear
Learning
Early Life Experience
Anxiety
title Safety learning during adolescence facilitates fear regulation in adult mice
title_full Safety learning during adolescence facilitates fear regulation in adult mice
title_fullStr Safety learning during adolescence facilitates fear regulation in adult mice
title_full_unstemmed Safety learning during adolescence facilitates fear regulation in adult mice
title_short Safety learning during adolescence facilitates fear regulation in adult mice
title_sort safety learning during adolescence facilitates fear regulation in adult mice
topic Adolescence
Safety
Fear
Learning
Early Life Experience
Anxiety
url http://www.sciencedirect.com/science/article/pii/S187892932500101X
work_keys_str_mv AT heidicmeyer safetylearningduringadolescencefacilitatesfearregulationinadultmice