Stress effects on the developing and adult brain Synaptic and network mechanisms underlying memory and disease

Stress can lastingly modulate experience-dependent changes in our brain that ultimately help to adapt our behavior. The capacity to encode, consolidate and later again retrieve information depends on brain plasticity, which occurs at many different levels ranging from synaptic to cellular and network changes. While generally adaptive in nature, stress also renders the brain vulnerable to psychopathologies, like post-traumatic stress disorder and neurodegenerative disorders, like Alzheimer’s Disease (AD).
The first part of this thesis investigates how acute stress influences recent and remote memories in the adult mouse brain. Specifically, we investigated how glucocorticoid hormones affect physical memory traces (i.e. engram cells) and show they enhance the generalization of memories. We also studied how these hormones may disrupt network connectivity to impair remote memory retrieval.
The second part of this thesis concerns the lasting effects of exposure to chronic stress early in life. Firstly, the effects of early life stress (ELS) on synaptic function and composition were investigated in the young and adult mouse brain. Secondly, we investigated the effects of ELS on synaptic function, composition and cognition in a mouse model of early AD pathology. Finally, in the same AD model, we assessed whether briefly blocking glucocorticoid signaling during the adolescent period can prevent the effects of ELS on later cognition.
Elucidating how stress affects the developing, adult and AD brain may provide mechanistic insights into how stress affects memory and disease susceptibility, which could aid the future development of therapeutic tools.