Holograms Reveal Brain's Inner Workings: Microscopy Technique Used to Observe Activity of Neurons Like Never Before

Holograms Reveal Brain's Inner Workings: Microscopy Technique Used to Observe Activity of Neurons Like Never Before

  9:36:00 AM    Science Lover

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Like far away galaxies, powerful tools are required to bring the minute inner workings of neurons into focus. Borrowing a technique from materials science, a team of neurobiologists, psychiatrists, and advanced imaging specialists from Switzerland's EPLF and CHUV report in The Journal of Neuroscience how Digital Holographic Microscopy (DHM) can now be used to observe neuronal activity in real-time and in three dimensions -- with up to 50 times greater resolution than ever before. The application has immense potential for testing out new drugs to fight neurodegenerative diseases such as Alzheimer's and Parkinson's.

This is a 3-D image of living neuron taken by DHM 
technology. (Credit: Courtesy of Lyncée Tec)

Neurons come in various shapes and are transparent. To observe them in a Petri dish, scientists use florescent dyes that change the chemical composition and can skew results. Additionally, this technique is time consuming, often damages the cells, and only allows researchers to examine a few neurons at a time. But these newly published results show how DHM can bypass the limitations of existing techniques.

"DHM is a fundamentally novel application for studying neurons with a slew of advantages over traditional microscopes," explains Pierre Magistretti of EPFL's Brain Mind Institute and a lead author of the paper. "It is non-invasive, allowing for extended observation of neural processes without the need for electrodes or dyes that damage cells."

Senior team member Pierre Marquet adds, "DHM gives precious information not only about the shape of neurons, but also about their dynamics and activity, and the technique creates 3D navigable images and increases the precision from 500 nanometers in traditional microscopes to a scale of 10 nanometers."

A good way to understand how DHM works is to imagine a large rock in an ocean of perfectly regular waves. As the waves deform around the rock and come out the other side, they carry information about the rock's shape. This information can be extracted by comparing it to waves that did not smash up against the rock, and an image of the rock can be reconstructed. DHM does this with a laser beam by pointing a single wavelength at an object, collecting the distorted wave on the other side, and comparing it to a reference beam. A computer then numerically reconstructs a 3D image of the object -- in this case neurons -- using an algorithm developed by the authors. In addition, the laser beam travels through the transparent cells and important information about their internal composition is obtained.



Normally applied to detect minute defects in materials, Magistretti, along with DHM pioneer and EPFL professor in the Advanced Photonics Laboratory, Christian Depeursinge, decided to use DHM for neurobiological applications. In the study, their group induced an electric charge in a culture of neurons using glutamate, the main neurotransmitter in the brain. This charge transfer carries water inside the neurons and changes their optical properties in a way that can be detected only by DHM. Thus, the technique accurately visualizes the electrical activities of hundreds of neurons simultaneously, in real-time, without damaging them with electrodes, which can only record activity from a few neurons at a time.

A major advance for pharmaceutical research

Without the need to introduce dyes or electrodes, DHM can be applied to High Content Screening -- the screening of thousands of new pharmacological molecules. This advance has important ramifications for the discovery of new drugs that combat or prevent neurodegenerative diseases such as Parkinson's and Alzheimer's, since new molecules can be tested more quickly and in greater numbers.

"Due to the technique's precision, speed, and lack of invasiveness, it is possible to track minute changes in neuron properties in relation to an applied test drug and allow for a better understanding of what is happening, especially in predicting neuronal death," Magistretti says. "What normally would take 12 hours in the lab can now be done in 15 to 30 minutes, greatly decreasing the time it takes for researchers to know if a drug is effective or not."

The promise of this technique for High Content Screening has already resulted in a start-up company at EPFL called LynceeTec (www.lynceetec.com).

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Human Brain Could Be Replicated In 10 Years, Researcher Predicts

Human Brain Could Be Replicated In 10 Years, Researcher Predicts

  10:54:00 AM    Science Lover

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A model that replicates the functions of the human brain is feasible in 10 years according to neuroscientist Professor Henry Markram of the Brain Mind Institute in Switzerland. "I absolutely believe it is technically and biologically possible. The only uncertainty is financial. It is an extremely expensive project and not all is yet secured."

Activity in the brain's neocortex is tightly controlled by
inhibitory neurons shown here which prevent epilepsy.
(Credit: Blue Brain Project; Ecole Polytechnique Federale de Lausanne)

The apparent complexity of the human mind is not a barrier to building a 'replica' brain claims Professor Markram. "The brain is of course extremely complex because it has trillions of synapses, billions of neurons, millions of proteins, and thousands of genes. But they are still finite in number. Today's technology is already highly sophisticated and it allows us to reverse engineer the brain rapidly." An example of the capability already in place is that today's robots can do screenings and mappings tens of thousands of times faster than human scientists and technicians.

Another hurdle on the path to a model human brain is that 100 years of neuroscience discovery has led to millions of fragments of data and knowledge that have never been brought together and exploited fully. "Actually no one even knows what we already understand about the brain," says Professor Markram. "A model would serve to bring this all together and then allow anyone to test whatever theory you want about the brain. The biggest challenge is to understand how electrical-magnetic-chemical patterns in the brain convert into our perception of reality. We think we see with our eyes, but in fact most of what we 'see' is generated as a projection by your brain. So what are we actually looking at when we look at something 'outside' of us?"

For Professor Markram, the most exciting part of his research is putting together the hundreds of thousands of small pieces of data that his lab has collected over the past 15 years, and seeing what a microcircuit of the brain looks like. "When we first switched it on it already started to display some interesting emergent properties. But this is just the beginning because we know now that it is possible to build it. As we progress we are learning about design secrets of our brains which were unimaginable before. In fact the brain uses some simple rules to solve highly complex problems and extracting each of these rules one by one is very exciting. For example we have been surprised at finding simple design principles that allow billions of neurons to connect to each other. I think we will understand how the brain is designed and works before we have finished building it."

The opportunities for this neuroscience research challenge are immense explains Professor Markram: "A brain model will sit on a massive supercomputer and serve as a kind of educational and diagnostic service to society. As the industrial revolution in science progresses we will generate more data than anyone can track or any computer can store, so models that can absorb it are simply unavoidable. It is also essential to build models when it comes to treating brain diseases affecting around two billion people. At present, there is no brain disease for which we really understand what has gone wrong in the processing, in the circuits, neurons or synapses. It is also important if we are to replace the need for the millions of animal experiments each year for brain research."

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Thought-propelled wheelchairs, soon

Thought-propelled wheelchairs, soon

  8:50:00 PM    Science Lover

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Italian researchers are in talks with manufacturers to make the system an affordable and common-place reality in the next 5-10 years

The user is connected via electrodes on his scalp, and sends a signal by concentrating for a few seconds on a list of desired destination, displayed on a screen.

In a project spanning three years, Italian researchers at Milan’s Polytechnical Institute Artificial Intelligence and Robotics laboratory have developed a wheelchair that obeys mental signals sent via a computer.

The user, who is connected to a computer through electrodes on his or her scalp, can send signals to the wheelchair by concentrating for a few seconds on the name of the desired destination – kitchen, bedroom, bathroom – displayed on a screen.

The system then uses a preset program to take the user to the desired destination.

“We don’t read minds, but the brain signal that is sent,” said Professor Matteo Matteucci who was part of the project.

The chair, he informed, is also equipped with two laser beams that can detect obstacles.

The Milan lab is already in contact with companies that could produce a commercial prototype that could cater to quadriplegics, Matteucci disclosed.

“Still, it could take between five and 10 years for this system to be available widely,” he said, adding that such a wheelchair would cost only 10 per cent more than a classic motorised version.

Research to develop the so-called Brain Computer Interface began in the early 1980s around the world.

Professor Matteo Matteucci (right) and PhD student Bernardo Dal Seno, wearing a skullcap mounted with electrodes and wired to a computer as he sits on a special wheel chair. Italian boffins have developed a wheelchair that obeys mental signals sent to a computer.

Matteucci said a handful of other researchers were working on similar projects to his, including the Federal Polytechnic School in Lausanne, Switzerland.

“Eventually, a research consortium should be set up that will use all these projects as a basis for finding the best approach,” he said.

“We’ve now started work on getting the chair to operate outdoors using a GPS,” Matteucci added.

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