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Entry from: 04.03.2019
Category: News, Press Releases

A protein for learning

A protein called Unc13a is crucial for nerve cells to amplify the signal they send to downstream cells. The process of amplification is important for learning, but also to keep the nervous system functional after disturbances. This has been shown by researchers from the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) and the Freie Universität Berlin in fruit flies (Drosophila), and the results were recently published in the prestigious journal Nature Communications.

Unc13a as a regulator of synaptic signal transmission. Simplified scheme of learning processes (from left to right) in which synaptic transmission strength changes. This happens, for example, when more Unc13a is accumulated at the synapse (right): it becomes stronger because more neurotransmitter vesicles can be released. Illustration: Mathias Bohme, Meida Jusyte, Alexander Walter, FMP.

Nerve cells within the brain or ones that connect to muscles communicate chemically at their contact points, the so-called synapses: The transmitting cell releases bubbles filled with neurotransmitters, which are recognized in the downstream cell by specialized receptor molecules. It was already known that Unc13a defines the release sites for these small neurotransmitter bubbles or vesicles. Now the researchers around Dr. Alexander Walter investigated the role of the protein in the adaptation of synaptic strength.The brain stores information by modifying individual synapses so that they react more strongly to the same signal in the future. Mechanisms for this have hitherto been known, predominantly regarding the receiving cell.

On the other hand, such adjustments are also necessary to compensate and prevent failures. At certain synapses of fruit flies, for example, more vesicles are released when the receptor molecules in the downstream cell are blocked. The signal will regain its original strength within ten minutes - as long as the transmitting cell is functioning normally. And that's exactly what Unc13a is necessary for, as the current results show.The Berlin scientists deliberately disturbed the ability of the protein to take the right position in the synapse. Normal signal transmission was hardly affected, however, the ability to compensate for a decreased sensitivity of the receptor molecules was. Unc13a also plays a role in prolonged disturbance, as the researchers showed. Only when more of this protein was incorporated into the synapse could signal transmission still work.

"And then we became ambitious," says the study's lead Alexander Walter, "and together with the group of Dr. Sigrist from the Freie Universität Berlin conducted a learning experiment." In fruit flies, it is known which individual nerve cells are responsible for the learning of odors. If flies are trained to follow a particular scent, they learn it very quickly. That is, unless the researchers also interfered with the correct positioning of Unc13a in exactly these odor-learning nerve cells.

"The flow of information was still there, but hardly any change", Walter describes the same effect as before with the compensation of disturbances. At this point, it has a very concrete impact: "The flies could not learn anymore."The two synapses examined are quite different. They even use different neurotransmitters. This suggests that Unc13a could be fundamental to signal amplification at all synapses - and not just in the fruit flies. Very similar proteins have been detected in many animal species, including humans. A relative of Unc13a might just be helping you as a reader to store this information about Unc13a.

Source: Böhme, M.A., McCarthy, A.W., Grasskamp, A.T., Beuschel, C.B., Goel, P., Jusyte, M., Laber, D., Huang, S., Rey, U., Petzoldt, A.G., Lehmann, M., Göttfert, F., Haghighi, P., Hell, S.W., Owald, D., Dickman, D., Sigrist, S.J. und Walter A.M. 2019. Rapid active zone remodeling consolidates presynaptic potentiation. Nature Communications. 06. März 2019, DOI 10.1038/s41467-019-08977-6.

Contact person for further information:
Dr. Alexander M. Walter
Molecular and Theoretical Neuroscience
Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP)
Charité Campus MitteCharitéplatz
10117 Berlin
Tel.: +49 (0)30-450-639-026
awalter@fmp-berlin.de

Öffentlichkeitsarbeit/Public Relations
Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP)
Silke Oßwald
Tel.: +49 30 94793 104
osswald(at)fmp-berlin.de

Das Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) gehört zum Forschungsverbund Berlin e.V. (FVB), einem Zusammenschluss von acht natur-, lebens- und umweltwissenschaftlichen Instituten in Berlin. In ihnen arbeiten mehr als 1.900 Mitarbeiter. Die vielfach ausgezeichneten Einrichtungen sind Mitglieder der Leibniz-Gemeinschaft. Entstanden ist der Forschungsverbund 1992 in einer einzigartigen historischen Situation aus der ehemaligen Akademie der Wissenschaften der DDR.