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The cell biology of neuronal plasticity: "looking backwards to see forwards"

English title The cell biology of neuronal plasticity: "looking backwards to see forwards"
Applicant Verkuyl J. Martin
Number 117328
Funding scheme Scientific Conferences
Research institution Friedrich Miescher Institute for Biomedical Research
Institution of higher education Institute Friedrich Miescher - FMI
Main discipline Neurophysiology and Brain Research
Start/End 01.04.2007 - 30.09.2007
Approved amount 5'000.00
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Lay Summary (English)

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Lay summary
The Cell Biology of Neuronal Plasticity: “Looking backwards to see forwards”Andrew Matus Retirement Symposium.Friederich Miescher Institute The Symposium was opened by the director of the Friederich Miescher Institute Prof Susan Gasser. She commemorated Prof Andrew Matus’ contribution to the FMI in particular and science in general. She gave a short overview of his long scientific career. She highlighted his major contributions, pointing out his work on microtubule associated proteins, which helped to understand the importants of the cytoskeleton in neurons, and his work on actin dynamics which drive spine plasticity. The latter was not possible without his pioneering role in the use of green fluorescent protein (GFP) in microscopy.The first speaker of the symposium was Prof Uno Lindberg from the Karolinska Institute in Stockholm, Sweden. He is like Andrew Matus an expert on the cytoskeleton. In his talk he pointed out that to understand the cytoskeleton we will have to view it from it role as a force generator that linked to transmembrane signal intracellular signal transduction. Therefore he preferred to revere to the actin cytoskeleton not as a skeleton but as the actin microfilament system, as it not only determines the structure of the cell but also determines its motility, is the barrier to the out side of the cell and plays a major role in transducing transmembrane signals. The second reason to call the actin cytoskeleton the actin microfilament system is that there is a multitude of proteins that interact and regulate the actin filaments such as for example the Arp2,3 complex, the inositol phosphate signaling and tropomyosin. He explained how tropomyosin initiates filament forming and counteracts the action of actin binding proteins such as gelsolin which sever the filaments.Prof Irwin Levitan from University of Pennsylvania, Philadelphia, USA continued the morning session and discussed how molecules explain neuronal excitability. He explained this by giving evidence gathered in his lab but he started out with experiments done by Hodgkin and Huxley. In the 1950-ies they showed in there experiments that during an action potential traveling thought the gaint squit axon sodium and potassium ions flow in and out of the axon trough the membrane. They concluded that these ions must move over the membrane through channels. Much later, the proteins making these channels were indeed found. In the late 90-ies crystals, were made from these proteins which helped to understand how these proteins from pores thought the membrane which can open and close by conformational changes. In the same decade Neher and Sakmann were able to record the currents flowing through single channels which made it possible to study the properties of the channels. How ever as Prof Irwin Levitan pointed out the channels are not just proteins in the membrane who function on there own. They are connected to many other proteins in the cytosol, including the cytoskeleton. To point out the importance of auxiliary proteins Prof Irwin Levitan discussed the example of Slo, a protein that regulates the function of potassium channels. Prof Heinrich Reichert of the Biozentrum in Basel in his talk entitled ‘Evolution of the bilateral brain’, took the position that just as we have learned from Copernicus that we are not the centre of the universe we humans should not think that our brains are any special. Like Vesalius we should study the evidence by taking a close look and not rely on what has been written. Based on comparative neuroanatomic which started with Cajal, the brians vertebrates (including mice and humans) look very different that those of invertebrates (such as insects, including the much studies Drosophila), however with the introduction of modern biology we can have a closer look at the development of these brains and compare the genes that orchestra the construction of the brain. When we do this, we find that the “blueprint” of these brains are in fact not very different from each other. Prof Reichert discussed four transcription factors involved in the development of the brain, namely the Hox, otd/Otx, Pax and columnar genes. These genes determine where parts of the body and thus the brain are formed along the anterioposterior and dorsoventral axis of the body. The temporal and spatial expression of these genes is extremely conserved from Drosophila to mice. In fact genes from vertebrates can rescue the function of the knock-out of the same gene in a invertebrate. Prof Aryeth Routtenberg, of Northwestern University Chicago, USA made us think about the paradoxes and contradictions of synaptic plasticity and long term memory. He explained that in his view the postulate of Hebb, stating that repeated persistent activity between to connected cells leads to a metabolic change strengthens the connection between the two cells, has now been (wrongly) translated in a two phase model of memory. The two phases are distinguished based on there protein synthesis dependency, the first phase which is protein synthesis independent is followed by a protein dependent phase. The initial phase is transient and the long term form of memory requires protein synthesis. However, Prof Routtenberg argues that the protein synthesis is non instructive and has only a role in replenishing the protein pool. In his view we have to accept the contradiction that protein modifications are sufficient for the formation of long lasting memory. The paradox is how structures so labile as synaptic contacts, as Andrew Matus and others have shown, and which is build up out of proteins that have a high turnover rate can lead to long lasting stable memories. Prof Craig Garner, of Stanford University Palo Alto, USA instructed use how to make sense of the complexity of proteins in the synapse, how to distinguish the trees from the forest. His approach is to think of the proteins as parts of larger units and to look beyond the individual proteins. He gave examples of units in the pre- and post synaptic terminal, and how some of parts of these units are transported on vesicles.Last but not least Prof Andrew Matus discussed whether we can explain minds with molecules. He started of by showing the paradigm shift had has occurred in thinking about the brain and behavior, from Freud who thought that you could understand how the mind works by talking to the experiments of skinner how considered the brain a black box, which could be understood by examining the input out put relation, to the approach of modern neurosciences which tries to understand the brain by looking at its structure and molecules. Prof Andrew Matus used accomplishments of his career to illustrate the approaches of modern neurobiology. He concludes his talk by noting that yes molecules can explain minds but will not solve the problem of what the mind is.
Direct link to Lay Summary Last update: 21.02.2013

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