A glance into a new world for neuroscience: research team from Göttingen led by Prof. Dr. Silvio O. Rizzoli present the first scientifically accurate 3D model of a synapse. Published May 30th 2014 in SCIENCE.
Synapses are the contacts between nerve cells that allow the flow of information that makes our brains work. However, the molecular architecture of these highly complex structures has been unknown until now. A research team from Göttingen, led by Prof. Silvio O. Rizzoli from the DFG Research Center and Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB) of the University Medical Center Göttingen, managed to determine the copy numbers and positions of all important building blocks of a synapse for the first time.
This allowed them to reconstruct the first scientifically accurate 3D model of a synapse. This effort has been made possible only by a collaboration of specialists in electron microscopy, super-resolution light microscopy (STED), mass spectrometry, and quantitative biochemistry from the UMG, the Max Planck Institute for Biophysical Chemistry, Göttingen, and the Leibniz Institute for Molecular Pharmacology, Berlin.
The project was funded by the European Research Council (ERC) and the Deutsche Forschungsgemeinschaft (DFG). The results have been published in the renowned scientific journal SCIENCE on May 30th 2014. Highlighting the impact of this work, the presented model has been selected as the cover of the respective issue of the SCIENCE journal.
Wilhelm BG, Mandad S, Truckenbrodt S, Kröhnert K, Schäfer C, Rammner B, Koo SJ, Claßen GA, Krauss M, Haucke V, Urlaub H, Rizzoli SO (2014) Composition of isolated synaptic boutons reveals the amounts of vesicle trafficking proteins. SCIENCE, May 30th, 2014. 344(6187): 1023-1028. DOI: 10.1126/science.1252884.
A New and Undiscovered Land in Neuroscience
“This 3D model of a synapse opens a new world for neuroscientists,” says Prof. Rizzoli, senior author of the publication. Particularly the abundance and distribution of the building blocks have long been terra incognita, an undiscovered land. The model presented by Prof. Rizzoli and his team now shows several hundreds of thousands of individual proteins in correct copy numbers and at their exact localisation within the nerve cell.
“The new model shows, for the first time, that widely different numbers of proteins are needed for the different processes occurring in the synapse,” says Dr. Benjamin G. Wilhelm, first author of the publication. The new findings reveal: proteins involved in the release of messenger substances (neurotransmitters) from so called synaptic vesicles are present in up to 26,000 copies per synapse. Proteins involved in the opposite process, the recycling of synaptic vesicles, on the other hand, are present in only 1,000-4,000 copies per synapse.
These details help to solve a long-lasting controversy in neuroscience: how many synaptic vesicles within the synapse can be used simultaneously? Apparently, more than enough proteins are present to ensure vesicle release, but the proteins for vesicle recycling are sufficient for only 7-11% of all vesicles in the synapse. This means that the majority of vesicles in the synapse cannot be used simultaneously.
The most important insight the new model reveals, is however that the copy numbers of proteins involved in the same process scale to an astonishingly high degree. The building blocks of the cell are tightly coordinated to fit together in number, comparable to a highly efficient machinery. This is a very surprising finding and it remains entirely unclear how the cell manages to coordinate the copy numbers of proteins involved in the same process so closely.
The new model will serve as a reference source for neuroscientists of all specialisations in the future, and will support future research, since the copy number of proteins can be an important indicator for their relevance. But the research team led by Prof. Rizzoli does not plan to stop there: “Our ultimate goal is to reconstruct an entire nerve cell”. Combined with functional studies on the interaction of individual proteins this would allow to simulate cellular function in the future – the creation of a “virtual cell”.
An impressive video animation has been created from the obtained data to visualise the structure and protein distribution of a synapse (http://www.sciencemag.org/content/344/6187/1023/suppl/DC1).
For his approach to study the molecular anatomy of nerve cells, Prof. Rizzoli has already been awarded an ERC Consolidator Grant 2013. "The findings of Prof. Rizzoli are spectacular", says Prof. Dr. Heyo Kroemer, Speaker of the UMG board and dean of the Faculty of Medicine. "This highly precise synaptic model will provide completely new possibilities for medical research. This is another example demonstrating that the University Medical Center Göttingen provides attractive conditions for international top-level research." Prof. Mathias Bähr, one of the CNMPB speakers, says “We are very excited that Prof. Rizzoli succeeded in accomplishing this project so fast. This study significantly advances our general understanding of the protein distribution within healthy nerve cells. In the future, these findings will contribute to identify anomalies in neuronal anatomy in neurodegenerative diseases, such as Parkinson’s disease.”
Prof. Dr. Silvio O. Rizzoli
Dept. Neuro- and Sensory Physiology, University Medical Center Göttingen European Neuroscience Institute (ENI) Göttingen
Grisebachstraße 5, 37077 Göttingen
Phone: +49 (0) 551 39-33630
CNMPB – Center for Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 – DFG Research Center 103
Dr. Heike Conrad
Scientific Coordination / Press & Public Relations
Humboldtallee 23, 37073 Göttingen
Telefon 0551 / 39-7065, email@example.com
http://www.rizzoli-lab.de - research group of Prof. Rizzoli
http://www.cnmpb.de – DFG Research Center and Cluster of
http://Excellence Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB) -
http://www.sciencemag.org/content/344/6187/1023/suppl/DC1 - video animation
Dr. Heike Conrad | idw - Informationsdienst Wissenschaft
27.03.2015 | Oak Ridge National Laboratory
How did the chicken cross the sea?
27.03.2015 | Michigan State University
In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...
The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.
As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...
When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.
The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe.
Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...
Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.
From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...
25.03.2015 | Event News
19.03.2015 | Event News
17.03.2015 | Event News
27.03.2015 | Agricultural and Forestry Science
27.03.2015 | Materials Sciences
27.03.2015 | Ecology, The Environment and Conservation