Psychiatric disorders are among the most common causes of years lived with disability. Yet, we lack a solid understanding of their onset and course, and current treatments are unsatisfactory. To offset this predicament, the study of critical periods (CPs) of development sets the focus on the roots of psychiatric disorders, when susceptibility to these illnesses is being installed but not yet set off, in order to better understand the underlying mechanisms.Recently, we identified in mice the CP of a brain circuit, the Habenulo-Interpeduncular-OTX2-Positive-System (HIPOPS), regarding stress response. Chronic Stress (CS) during this CP strongly activates the HIPOPS and installs a susceptibility to anxiety. Subsequently, a second round of CS during adulthood is required to trigger anxiety-like symptoms. These phenotypes are specific of the HIPOPS since genetic modifications of this circuit abolished the behavioral and molecular phenotypes.However, the underlying mechanisms remained elusive, and our stress protocol yielded divergent results between male and female mice. This led us to further investigate the HIPOPS’ CP in both sexes, which revealed differences in the HIPOPS’ stress reactivity between juvenile males and females. Additionally, we identified Perineuronal Nets (PNNs) in the HIPOPS, which are key actors of CPs, that mature at distinct rates between both sexes. Taken together, these results suggest different windows of CPs regarding HIPOPS’ stress response in males and females. With the addition of ongoing experiments, our study aims uncover the potential role of PNNs in HIPOPS-mediated susceptibility to anxiety and elucidate the sexual dimorphism associated with this phenotype.