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AMPA receptors on cell membrane make us smarter

02 September 2009 NWO (Netherlands Organization for Scientific Research)

AMPA receptors are an important regulating factor in the connection between our nerve cells. However, Dutch researcher Helmut Kessels has demonstrated that it is not the amount of AMPA receptors inside the cell that are vitally important but the receptors located on the cell membrane. Changes in the strength of the connections between two nerve cells form the basis of our ability to learn. The results of the research are published in the July issue of Nature Neuroscience.

The AMPA receptors influence our synaptic plasticity; the capacity of the connection (the synapse) between two nerve cells to change strength. To date it was assumed that an increase in the number of receptors in a cell could also bring about a change in the connections between nerve cells and therefore in our capacity to learn. Neurobiologist Kessels has now established that the synaptic plasticity is not dependent on the quantity of receptors in the cell, but the quantity of receptors located on the cell membrane. Therefore merely increasing the production of AMPA receptors is not enough to regulate the connections between nerve cells.

Stargazin and phosphorylation

Although an increased production of AMPA receptors generated a large quantity of receptors in the cell, these receptors were in turn degraded in lysosomes. Kessels investigated two subunits of AMPA receptors - GluR1 and GluR2 - each of which serve as a model of two groups of AMPA receptors that play a different role in how we learn. GluR1-containing receptors are crucial for the creation of new memories, while the receptors without GluR1 possibly play an important role in the storage of memories.

The researcher managed to prevent the lysosomal degradation of GluR1 by increasing the quantity of receptor-interacting protein stargazin at the same rate as the quantity of GluR1. The same effect was also achieved by phosphorylation of GluR1, a process in which a phosphate group was attached to the protein. However, a greater quantity of GluR1 in the cell did not increase the quantities of receptors on the cell membrane or in synapses. Yet this was the case for GluR2. With the help of phosphorylated stargazin, the quantity of GluR2 on the cell surface and in the synapses could be increased. Further research is needed to demonstrate whether this actually influences synaptic plasticity and perhaps our capacity to learn.
Helmut Kessels carried out his research at the Cold Spring Harbor Laboratory in New York. This was made possible by the Talent grant he received from NWO in 2004.

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