Stress and memory in health and disease Impact on Alzheimer's disease and memory mechanisms

Exposure to stressful experiences, either early or later in life, can have a strong impact on learning and memory in adult and ageing individuals. Early life experiences in particular have been implicated in determining the vulnerability and resilience for cognitive decline, for instance when the brain is already vulnerable, such as seen in Alzheimer’s disease (AD). The first aim of this thesis was to study the effects of experiences early in life (albeit positive or negative) on aging- or AD-related cognitive decline, and to better understand the underlying mechanisms. I particularly focused on the role of the hypothalamus-pituitary-adrenal (HPA)-axis, and on the expression and functionality of glutamate receptors in this process. The second aim of this thesis was to investigate why stressful memories are retained so well. Recent studies suggest that only a subset of neurons is required for any memory trace (‘engram cells’). Using novel genetic and molecular approaches, these engram cells were visualised, characterised and manipulated, to unveil effects of glucocorticoids on memory formation.