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Molecule holds fear at bay

Eph receptors link experiences with emotions

Munich, 08/20/2008

Linking experiences with emotions determines many aspects of our daily lives. It allows us to recognize pleasant things or avoid dangerous situations. This link arises when nerve cells create new or reinforce existing connections to one another. Scientists at the Max-Planck Institutes of Neurobiology and Psychiatry and the University Hospital Großhadern have now investigated a molecule that significantly influences the strength of these connections. (PNAS, 4. August 2008)

If a child touches a hotplate, it will most likely never repeat this action. The reason for this fast learning resides in the amygdala, a small area of the brain that links experiences to emotions. In the amygdala, the hotplate, the pain felt and a slight fear are all linked to one another – and renewed touching is avoided in the future. While this association of fear and experiences frequently protects the body from harm, an incorrect or disproportionate link can actually lead to major problems. In phobias for example, relatively harmless objects or situations are linked to fear. But how do the nerve cells create such links? And how are they regulated?

Memories and fear–experience associations arise when nerve cells create new contacts with their neighboring cells, or when they reinforce existing contacts. So-called Eph receptors are important for the transmission of signals at such contact points. These receptors sit on the surface of the nerve cells and act much like antennas. If a neighboring cell binds with its corresponding binding partners to these receptors, then the signal transmission is amplified. The fewer Eph receptors a cell has on its surface, the weaker the communication with other nerve cells becomes – linking of emotions and experiences in the amygdala becomes increasingly difficult.

Scientists at the Max-Planck Institutes of Neurobiology and Psychiatry and the University Hospital Großhadern have now investigated a molecule called Rin1 that controls the number of Eph receptors on the surface of nerve cells. Rin1 sees to it that more Eph receptors are transported from the surface into the cell. If Rin1 is completely absent from the nerve cells of the amygdala of a mouse, then the number of Eph receptors remains high. This results in intensified signal transmission between the nerve cells – the molecular basis for an increased fear response. If, by contrast, it is the Eph receptors that are missing, then communication between the nerve cells is not amplified, and one can expect the association of emotions and experiences to become difficult.

Rin1 is the first known molecule that limits the availability of Eph receptors in the adult brain. “We are gradually beginning to understand how emotions and experiences are linked at the molecular level,” states Rüdiger Klein, head of the study. Such an understanding is also crucial to the potential development of drugs. “Information obtained through basic research such as the recently demonstrated regulation of Eph receptors by Rin1 could allow us to improve deficient signal transmission between nerve cells, or to eliminate detrimental links in the future,” Katrin Deininger expresses her hope for the long-term results of her study. The chances are good, since Eph receptors also play an important part, for instance, in the development or regeneration of the nervous system. (sm, MPI)

Katrin Deininger, Matthias Eder, Edgar R. Kramer, Walter Zieglgänsberger, Hans-Ulrich Dodt, Klaus Dornmair, John Colicelli, Rüdiger Klein
“The Rab5 guanylate exchange factor Rin1 regulates endocytosis of the EphA4 receptor in mature excitatory neurons”
PNAS, 4 August 2008

Dr. Katrin Deininger
Max Planck Institute of Neurobiology, Martinsried
Tel.: ++49 (0) 89 / 8578-3181

Dr. Stefanie Merker
Max Planck Institute of Neurobiology, Martinsried
Public relations
Tel.: ++49 (0) 89/ 8578-3514
Fax: ++49 (0) 89 / 89950-022


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