Scientists headed by Matthias Schmidt working with mice at the Max Planck Institute of Psychiatry, Munich, Germany, have identified the molecular composition of the AMPA receptor, a common binding site in the central nervous system, as a possible cause of different reactions to ongoing exposure to stress.
The AMPA receptor in the brain is composed of four subunits, GluR1 to GluR4, and acts as a binding partner for the neurotransmitter glutamate. As an ion channel, it mediates the transmission of electric impulses between nerve cells and thus can influence perception, feelings, reactions and behaviour. The composition of the AMPA receptor is determined by both genetic and epigenetic (or environmental) factors. The specific composition of the receptor in terms of subunits GluR1 and GluR2 is important for its ability to allow calcium ions to flow into the cell, triggering an electrical impulse and altering neuronal communication in the brain.
The researchers have shown that stress-vulnerable mice have a low proportion of GluR1 and a high proportion of GluR2. Stress-resilient mice, in contrast, have only a low proportion of GluR2.
Behavioural studies reveal that the composition of the AMPA-receptor, and therefore stress resilience, correlates with measurable changes to short-term memory. Consequently, even in the absence of stress, a GluR2-rich AMPA receptor leads to altered neuronal activity and poor memory in mice.
If it were possible to use this correlation as a biomarker in humans to determine the composition of the AMPA receptor, it could help to predict individual risk for stress-related diseases.
(C) Image: Max Planck Institute of Psychiatry
- Individual stress Vulnerability Is Predicted by Short-Term Memory and AMPA Receptor Subunit Ratio in the Hippocampus,
Mathias V. Schmidt, Dietrich Trümbach, Peter Weber, Klaus Wagner, Sebastian H. Scharf, Claudia Liebl, Nicole Datson, Christian Namendorf, Tamara Gerlach, Claudia Kühne, Manfred Uhr, Jan M. Deussing, Wolfgang Wurst, Elisabeth B. Binder, Florian Holsboer, Marianne B. Müller
J. Neurosci. 2010.
- Max Planck Press Release