Winfried Denk, Arthur Konnerth, Karel Svoboda and David Tank win The Brain Prize

The Brain Prize has been awarded to four scientists: Winfried Denk, Arthur Konnerth, Karel Svoboda and David Tank.

The scientists will share the 1 million euro prize, to be presented on May 7 in Copenhagen by Crown Prince Frederik of Denmark, for their invention and development of two-photon microscopy, a transformative tool in brain research.

Two-photon microscopy has dramatically changed the way we study the brain. It combines advanced techniques from physics and biology to allow scientists to examine the finest structures of the brain in real time. Using this revolutionary technology, researchers are now able to examine the function of individual nerve cells with high precision, especially how nerve cells communicate with each other in networks. This is a huge step forward in the understanding of the physical mechanisms of the human brain and how the brain's networks process information. In addition, researchers have been able to follow how connections between nerve cells are established in the developing brain. It has led to the identification of signaling pathways that control communication between nerve cells and provide the basis for memory, and it has enabled the study of nerve cell activity in the networks that control vision, hearing and movement.

"It was exciting, and a lot of fun, to work with my colleagues awarded with this year's Brain Prize in the development and application of two-photon microscopy to the study of the nervous system," says David Tank.

Tank serves as director of the Simons Collaboration on the Global Brain, a multidisciplinary community of scientists focused on furthering our understanding of higher brain function. The group explores 'internal brain states'—the states that control motivation and decision bias, representations of remembered events and cognitive explorations. Using cutting-edge methodology, Global Brain investigators can record simultaneously from large numbers of neurons, allowing recognition of internal brain states from activity alone, unprecedented in the history of brain research. Two-photon microscopy is one of the core technologies used by Global Brain researchers in their work.

"Analysis of the data produced by this method provides new insights into the neural coding and dynamics underlying cognitive abilities like memory and decision-making, processes that the Simons Collaboration on the Global Brain aims to decode," Tank says.

"David Tank has been one of the most creative people in all of neuroscience for many years," says Gerald Fischbach, Chief Scientist and Fellow at the Simons Foundation. "His accomplishments, with the other awardees, have revolutionized the way we can visualize brain structures—and that is just the beginning. David's breadth is greatly valued in his leadership of the Simons Collaboration on the Global Brain, an effort that involves both theory and experiment in studies of internal brain states."

About two-photon microscopy

Two-photon microscopy uses an advanced form of fluorescence microscopy. In fluorescence microscopy, cell components are labeled with special molecules, which glow (fluoresce) when illuminated by light of a particular wavelength, usually UV light. The microscope then picks up the emitted fluorescent light. However, the short-wavelength, high-energy UV light tends to spread through the tissue, making more areas fluoresce and making it difficult to focus on a specific cell or cell part. Also, UV light cannot penetrate deep into the tissue, and because of its high energy quickly exhausts the fluorescent molecules.

Two-photon microscopy uses pulsed infrared lasers to focus the illumination only on the target area, which is the only area that then emits light. "It's like the difference between looking at a movie in daylight, and looking at a movie in a dark hall: If you take away the unwanted light, you can see what you want to see much better," says Maiken Nedergaard of the Center for Basic and Translational Science at Copenhagen University.

The two-photon principle allows the use of long-wavelength (low-energy) infrared light. Under normal circumstances, one photon of infrared light is not enough to elicit fluorescence. However, the pulsed laser can deliver a large amount of light to a specific point. Intermittently, two photons will hit a fluorescent molecule, which is sufficient to make it glow. The infrared light does not exhaust the fluorescent molecules as happens in conventional fluorescence microscopy. Infrared light can also go much deeper down into the tissue. This gives the technique its main advantage: For the first time, we can see real changes inside a living, active brain, even hundreds of micrometers below the brain surface (a human hair is around 90 micrometers thick).

Provided by Simons Foundation