Early life experience, stress-hormones and synaptic function
One of the current views of how memories are formed is that neurons are
activated during the learning process thereby changing the strength of
communication between neurons. To examine the molecular and cellular mechanisms
that underlie the memories for fearful events we focus on function and
properties of synapses. Since memory enhancing effects of stress are mediated by
hormones, such as norepinephrine and glucocorticoids - which are released during
stressful experiences - we study in detail how these hormones affect
(activity-dependent) synaptic plasticity and whether these effects underlie
their memory enhancing effects.
A second important research line involves the question why some individuals
remember (fearful) information better than others. This topic is directly aimed
to get a better understanding of risk factors to develop cognitive deficits such
as PTSD or anxiety. Epidemiologic studies suggest that early life events might
increase the risk to develop psychopathology) e.g. depression, but also anxiety)
at later age. We therefore use animal studies which allow direct analysis of how
early life events and maternal care affect synaptic function and memory
processes at adult age.
In a third line we examine synaptic structure and function in relationship
to dementia. Alzheimer’s disease (AD) is characterized by early impairments in
learning and memory processes resulting in loss of higher cognitive functions.
In addition to A?-containing plaques, neurofibrillary tangles (NFT) are a
prominent intracellular hallmark of AD. NFTs are composed primarily of
hyperphosphorylated Tau protein that has polymerized into straight and
paired-helical filaments. Importantly, pathological deregulation of Tau
phosphorylation correlates well with dementia in AD and appears to precede
polymerization and NFT formation. We examine, using a multidisciplinary
approach, how Tau affects hippocampal synaptic function and structure, two most
relevant endpoints for learning and memory.