Research line dr. H.J. (Harm) Krugers

Early life experience, stress-hormones and synaptic function

  1. 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.
  2. 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.
  3. 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.

10 December 2012