Controlling transmitter glutamate

1. Disorders afflicting the nervous system account for more hospitalizations, more long-term care, and more chronic suffering than nearly all other disorders combined (Cowan and Kandel, 2001). The emotional and economic losses are enormous.

2. Effective treatment is mostly unavailable, and prevention is difficult due to insufficient understanding of the causes.

3. When brain tissue is diseased, complex processes start and nerve cells often continue to die after the initiating stimulus has stopped.

4. Among the most exciting mechanisms are those controlling extracellular glutamate. Evidence suggests they play key roles in the disease processes ultimately leading to the nerve cell damage, disabilities and suffering (for review see: Danbolt, 2001).

Challenge: The mechanisms controlling glutamate are hard to study because glutamate is involved in so many different and interconnected processes. Glutamate mediates most of the excitatory (stimulating, activating) signals in the central nervous system. This does not only include signals involved in perception, cognition and movements, but also for cell survival, elimination, migration and differentiation, as well as for synapse formation and elimination. Further, glutamate affects brain energy consumption, free radical formation, cell volume and water transport. Whenever brain tissue is studied, it changes.

Strenght: Our group has expertise in the construction of transgenic animals, membrane protein purification and reconstitution in artificial cell membranes, neuropharmacology, confocal imaging, electron microscopy, antibody production, and advanced databasing. We are part of Norway's largest center of excellence (CMBN) and have close ties to the other bio-medical center of excellence in Norway Centre for the Biology of Memory) and to the Norwegian Center for Stem Cell Research. We thereby have on site access to expertise in stem cells, growth factors, in vivo and in vitro electrophysiology, protein sequencing, animal NMR and PET scans, fibre tracing, 3-D reconstruction, computational neuroscience, and behavioral testing.