Scientists under the leadership of the University of Bonn have harnessed rabies viruses for assessing the connectivity of nerve cell transplants: coupled with a green fluorescent protein, the viruses show where replacement cells engrafted into mouse brains have connected to the host neural network. A clearing procedure which turns the brain into a ‘glass-like state’ and light sheet fluorescence microscopy are used to visualize host-graft connections in a whole-brain preparation. The approach opens exciting prospects for predicting and optimizing the ability of neural transplants to functionally integrate into a host nervous system. The results have been published in “Nature Communications”.
Many diseases and injuries result in a loss of nerve cells. Scientists are working on tackling this challenge by transplanting neurons. In Parkinson’s disease, for instance, this is attempted with implanted dopamine-producing nerve cells.
The key question for such techniques is whether the implanted cells actually connect with the existing neural network of the host brain and thus compensate the functional loss. “Previous methods only provided an incomplete or very small-scale insight into the functional integration of implanted neurons in the brain,” says Prof. Oliver Brüstle from the Institute of Reconstructive Neurobiology at the University of Bonn and LIFE & BRAIN GmbH.
Exploiting viral spreading across neurons
Together with scientists of various disciplines at the University of Bonn and cooperation partners from Cologne and Chicago (USA), the team led by Prof. Brüstle developed a new technique: “This enables the connection of implanted cells in the entire brain to be visualized in high resolution.” The basis of this technology is provided by genetically altered rabies viruses.
The researchers are exploiting the fact that these viruses spread backwards via nerve cell junctions – called synapses. The genetically altered rabies virus, which is no longer dangerous to humans, carries a fluorescent protein. Upon infection of the graft, the transplanted neurons turn green. At the same time, the ‘green’ virus spreads backwards across established synapses to connected host neurons, which are also turning green.
A three-dimensional nerve circuit diagram across a transparent brain
To visualize the labeled cells, the team first employed a special clearing procedure. “This technique makes it possible to turn the brains completely transparent – almost as glass,” says Dr. Martin Schwarz from the Bonn Department of Epileptology, who perfected this technique. The transparent brain is then studied layer by layer, similar to computer tomography, using what is known as a light sheet fluorescence microscope, which Prof. Ulrich Kubitscheck and his team at the Institute for Physical and Theoretical Chemistry at the University of Bonn developed specifically for this purpose.
“With this technique, the brain is scanned in high resolution in over 1,000 virtual optical sections; the data is then reconstructed three-dimensionally,” explains Prof. Kubitscheck. “As the implanted neurons and the recipient’s nerve cells connected to them light up green, a three-dimensional brain map can be created that delineates all the recipient cells connected to the transplant – the graft connectome,” says Dr. Jonas Doerr, who first-authored the study together with Martin Schwarz.
As the brain tissue itself becomes invisible after the clearing procedure, the researchers in a last step aligned the fluorescent maps with neuroanatomical data generated via magnetic resonance tomography of mouse brains. “Similar to cities on a globe, all of the cells marked in green can thus be allocated to distinct anatomical territories,” says Prof. Mathias Hoehn from the Max Planck Institute for Metabolism Research in Cologne, whose group conducted these calculations.
Great potential for the development of nerve cell transplants
“Our findings show that the transplanted neurons integrate in a remarkably region-specific manner into the different transplant sites,” reports Prof. Brüstle. The researchers hope that the new approach will be particularly useful for studying and optimizing the ability of neuronal transplants to connect with the host brain before they are used for clinical therapy. As a next step, they plan to use the rabies system to investigate how human dopamine-producing cells can be best wired into the brain of mice with induced Parkinson-like symptoms.
Publication: Whole-brain 3D mapping of human neural transplant innervation, Nature Communications, DOI: 10.1038/ncomms14162
Prof. Oliver Brüstle
Institute of Reconstructive Neurobiology
University of Bonn
LIFE & BRAIN GmbH
Tel. +49 (0)228/6885500
Johannes Seiler | idw - Informationsdienst Wissenschaft
New study points the way to therapy for rare cancer that targets the young
22.11.2017 | Rockefeller University
Penn study identifies new malaria parasites in wild bonobos
21.11.2017 | University of Pennsylvania School of Medicine
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
22.11.2017 | Medical Engineering
22.11.2017 | Materials Sciences
22.11.2017 | Health and Medicine