AUTHOR=Williams Robert , Van Den Oord Charlie , Lee Erica N. , Fedde Samuel C. , Oscherwitz Gia L. , Ribic Adema TITLE=Critical period plasticity is associated with resilience to short unpredictable stress JOURNAL=Frontiers in Behavioral Neuroscience VOLUME=Volume 19 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2025.1584240 DOI=10.3389/fnbeh.2025.1584240 ISSN=1662-5153 ABSTRACT=Low resilience to stressful events can increase the risk of anxiety and depression. Resilience decreases with age, parallel to drastic changes in the quality of brain plasticity from juvenile to old age, suggesting that the type of plasticity found in the maturing brain promotes resilience. To indirectly test this, we administered short unpredictable stress to adult male and female wild type (WT) C57BL/6 mice, as well as to two groups of mice characterized by heightened cortical plasticity: adolescent C57BL/6 WT mice and adult mice that lack SynCAM 1 (Synaptic Cell Adhesion Molecule 1), a critical plasticity brake in the mature brain. We found that short unpredictable stress robustly increased core body temperature in all groups of mice, indicative of stress-induced hyperthermia (SIH) and confirming the efficacy of the stress paradigm. However, depressive-like behavior as measured though tail suspension test was increased in adult WT mice only, supporting that the type of plasticity found in the immature brains of adolescent WT and adult SynCAM 1 knockout (KO) mice promotes resilience to stress. All three groups of mice showed a mild increase in locomotor activity after stress, suggesting that the quality of plasticity does not correlate with resilience to anxiety-like phenotypes. Our study hence provides indirect evidence for the protective role of developmental plasticity during stress and points to new mechanisms that promote resilience to stress-induced depression.