A €1 million European neuroscience research prize has been awarded to the inventors of two-photon microscopy, a technique which has transformed the way the brain is studied. Recognising scientists who have made outstanding contributions to European neuroscience, the Brain Prize highlights the impact two-photon microscopy has had for researching diseases such as Alzheimer’s as well as for observing brain behaviour.
The four scientists, Winfried Denk and Arthur Konnerth from Germany, and Karel Svoboda and David Tank from the USA, will be presented with the award by His Royal Highness Crown Prince Frederik of Denmark at a ceremony due to take place in Copenhagen on 7 May.
Two-photon microscopy has dramatically changed the way the brain is studied, allowing scientists to examine three-dimensional images of biological specimens in real time.
The technique uses an advanced form of fluorescence microscopy, whereby cell components are labelled with molecules that fluoresce under ultraviolet light, which are then observed using a microscope. However, the short-wavelength, high-energy UV-light used for this more conventional method spreads through the tissue, making it difficult to focus upon a specific cell or cell part.
Two-photon microscopy uses pulsed infrared lasers to focus the illumination on the target area, so that only the biological components of interest fluoresce light.
And, unlike conventional fluorescence microscopy, the infrared light does not exhaust the fluorescent molecules. Furthermore, infrared light can go much deeper down into the tissue, meaning that scientists can observe real changes inside a living, active brain, even down to hundreds of micrometres below the brain surface.
Using this technology, researchers are now able to examine the function of individual nerve cells and they communicate with each other in networks. This is a huge step forward in the understanding of the physical mechanisms of the human brain and in the understanding of how the brain’s networks process information.
This technique has already led to identification of signalling pathways that control communication between nerve cells and provide the basis for memory, and it has enabled the study of nerve cell activity in those networks that controls vision, hearing and movement.
‘Thanks to these four scientists we’re now able to study the normal brain's development and attempt to understand what goes wrong when we're affected by destructive diseases such as Alzheimer’s and other types of dementia. More than that, we are able to visualise how adaptive behavioural changes affect the nerve cells of living animals,’ explained Professor Povl Krogsgaard-Larsen, chair of Grete Lundbeck European Brain Research Foundation, which awards The Brain Prize.
Winfried Denk was the driving force behind the invention. Along with David Tank and Karel Svoboda, he used the technique as a tool to visualise activity at the level of the neurons' fundamental signalling units, the ‘dendritic spines’. Arthur Konnerth built on this invention to monitor the activity in thousands of synaptic connections in living animals simultaneously. Karel Svoboda went on to use two-photon microscopy to map the changes that occur in the brain's network when animals learn new skills.
Since its invention in 1990, two-photon microscopy has formed the basis of more than 10,000 research papers, not only in brain research but also in other areas of physiology, embryology and tissue engineering.
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