Shaping memories upon stress A behavioral, cellular, synaptic and molecular perspective on glucocorticoid modulation of learning and memory

Stress, particularly during early life, can profoundly alter the mechanisms of learning and memory by reshaping brain architecture. This dissertation investigates how early-life stress and acute corticosterone exposure influence fear memory processes, integrating behavioral, cellular, synaptic, and molecular perspectives. The first part explores the enduring, sex-dependent effects of early-life stress on fear acquisition and retrieval, highlighting adolescence as a potential intervention window and focusing on mediators such as excitation/inhibition balance, perineuronal nets, synaptic proteomics and engrams. Behavioral analyses are further complemented by advanced computational approaches to identify coping strategies and resilience patterns after early-life stress in a fearful memory task. The second part addresses glucocorticoid–memory interactions, emphasizing microglia and their glucocorticoid receptors as mediators of corticosterone-enhanced memory consolidation. This is approached through both a literature review and experimental work using a transgenic mouse model with inducible microglial glucocorticoid receptor depletion, revealing the contribution of microglial glucocorticoid signaling to stress hormone effects on memory. Together, this dissertation demonstrates the dynamic, context-dependent influence of stress hormones on cognition from a multilevel perspective and proposes new avenues for understanding how early-life stress and stress hormones shape memories.