„I am very grateful to my scientific mentors,“ Prof. Konnerth said, „and to TUM, where most of the work for which the prize was given was done.“ He first worked at TUM in 1999-2000, when he conducted an essential part of the award-winning research (published in 2003). In 2006 Konnerth became the founding chair of TUM’s Friedrich Schiedel Institute for Neuroscience. He is also a Carl von Linde Fellow of the TUM Institute for Advanced Study and a principal investigator in the Excellence Clusters SyNergy (Munich Cluster for Systems Neurology) and CIPSM (Center for Integrated Protein Science Munich).
TUM President Wolfgang A. Herrmann said, „Arthur Konnerth was a key faculty appointment when he returned to TUM in 2006 as Friedrich Schiedel Foundation chair. Ever since, he has been pivotal in developing TUM’s competence as a worldwide leading center of neuroscience research.“
Konnerth has led pioneering studies of how the brain works – in good health as well as under the effect of neurodegenerative diseases such as Alzheimer’s – from intra- and intercellular functioning to behavior. Several ground-breaking discoveries have been enabled by his use of optical techniques, including two-photon microscopy, that allow highly specific observation of brain activity in living animals.
The other recipients of the 2015 Brain Prize are Winfried Denk (Max Planck Institute of Neurobiology, Munich, Germany), David Tank (Princeton University, New Jersey, USA), and Karel Svoboda (Howard Hughes Medical Institute, Maryland, USA). The million-euro award is a personal prize, to be shared equally among the awardees. It will be presented in Copenhagen on May 7 by Crown Prince Frederik of Denmark.
From cells to circuits, in illness as well as health
In 2003 Konnerth and colleagues pioneered an imaging method that permitted for the first time the analysis of cortical circuits with single-cell resolution. This method is nowadays used in many laboratories worldwide to improve our understanding of how the brain controls behavior in animals. More recently they further improved their method, allowing them in 2010 to observe a mouse in the act of seeing, with resolution that went beyond a single nerve cell to a single synapse. They combined two-photon fluorescent microscopy – making it possible to look up to half a millimeter into brain tissue and view not only an individual cell, but even its fine dendrites – with the so-called patch-clamp technique, which let them conduct electrical signals to individual dendrites. This study showed for the first time that an individual neuron integrates input representing multiple sensory features into a well-defined, unique output signal: a decision, in essence, made automatically by a single nerve cell.
Another key discovery came in 2012, from in vivo single-neuron experiments with a mouse model of Alzheimer’s disease. Konnerth’s group observed correlations between increases in both soluble and plaque-forming beta-amyloid – a protein implicated in the disease process – and dysfunctional developments on several levels: individual cortical neurons, neuronal circuits, sensory cognition, and behavior. Their results showed that these changes progress in parallel and that, together, they reveal distinct stages in Alzheimer’s disease with a specific order in time.
In 2013, a combination of optical techniques shed light on the brain’s „slow waves,“ rhythmic signal pulses that sweep through the brain during sleep and are assumed to play a role in processes such as the consolidation of memory. The slow waves can be observed in very early stages of development, and they may be disrupted in Alzheimer’s and other diseases. In this study, two-photon microscopy was used in conjunction with optogenetics, an approach that enabled spatially defined stimulation of small numbers of neurons. Konnerth’s group showed conclusively that slow waves start in the cerebral cortex, ruling out other long-standing hypotheses. The researchers also found that such a wave can be set in motion by a single tiny cluster of neurons. „Out of the billions of cells in the brain,“ Konnerth explained, „it takes not more than a local cluster of fifty to one hundred neurons in a deep layer of the cortex, called layer 5, to make a wave that extends over the entire brain.“
Prof. Konnerth’s research has been supported by the German Research Foundation (DFG), the European Research Council, and the Friedrich Schiedel Foundation.
Prof. Arthur Konnerth
Technische Universität München
Institute for Neuroscience