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Daniel Durstewitz

Bernstein Center Heidelberg-Mannheim,
Central Institute of Mental Health

Saturday evening, just before closing time – how do we know in which butcher shop of the town we will still be most likely to get a Sunday roast? And how are we able to remember the shopping list with the side dishes that we have just bought at the supermarket? Working memory, decision-making, learning of implicit rules and anticipation of events as parts of higher behavioral performances belong to the research areas of Daniel Durstewitz. He investigates how these behaviors are neurally implemented and what happens when these processes are disturbed in mental diseases. Since May 2010, Durstewitz has been the coordinator of the new Bernstein Center Heidelberg-Mannheim.

Daniel Durstewitz

A native of Lower Saxony, Durstewitz studied psychology and later on also computer science at Technische Universität Berlin. During his PhD studies in the lab of Onur Güntürkün at Ruhr-University Bochum he came in closer contact with neurobiology. For his investigations of the prefrontal cortex, he carried out biophysical modeling of prefrontal neurons and networks and also conducted behavioral experiments in pigeons and neuroanatomical studies. Since that time, he has been particularly interested in the bridge between the diverse micro- and macroscopic levels of nervous system description. How do specific ion channels affect the transfer function of single neurons, and how does that in turn impact on the dynamics of the entire neural network? How does the activity of these networks then ultimately lead to observable behavior? Analyzing the connection between the different description levels—molecule, cell, network, behavior—is the primary goal of Durstewitz‘ research. „In my mind, we have to understand the structural and biophysical basis of neuronal dynamics in order to bridge the gap between physical processes in the brain and behavior,“ says the scientist.

With his PhD in the bag, Daniel Durstewitz relocated for two years to the Computational Neurobiology Lab at the Salk Institute for Biological Studies in La Jolla, USA. „The lighthearted explor-atory creativeness in American science and the tremendous importance of an interdisciplinary, non-hierarchical and open discussion culture for the generation of new ideas has strongly influenced my own attitude,“ says Durstewitz. At the Salk, he deepened his knowledge in theoretical research on neural processing using dynamic system approaches and learned electrophysiological techniques. At the beginning of the millennium he returned to Bochum where he was the head of the Emmy Noether Research Group „Computational Neuroscience“ until he was offered a faculty position at the University of Plymouth in England in 2005.

Since 2008, Durstewitz has been working at the Central Institute of Mental Health (CIMH), based in Mannheim, where he and his team have established the field of computational neuroscience on site. One of his main work areas comprises the mathematical modeling of neurons and neural networks, such as the prefrontal cortex and hippocampus, which are associated with higher cognitive functions. Although in the past Durstewitz had primarily been interested in higher cognition from a basic science perspective, working at the CIMH has shifted his focus more to medical aspects. For his projects within the Bernstein Center, the 46-year-old neuroscientist examines dysfunctions of the prefrontal cortex and the hippocampus as in schizophrenia or depression.

One of his major research areas consists in the study of the molecular and genetic determinants of cognitive dysfunction in these diseases. By means of computer models, Durstewitz’ group simulates the effects of certain risk genes on neural dynamics. The gene CACNA1C, for example, encodes a subunit of high-voltage-gated calcium channels. Distinct gene variants are associated with different conductivities of this channel and thus carry varying risk for schizophrenia. Using statistical data analysis from the viewpoint of nonlinear dynamics and machine learning, Durstewitz also tries to reconstruct network dynamics from experimental data to analyze in detail the consequences of different calcium channel variants on—for instance—neuronal attractor states and oscillations in the prefrontal cortex.

Another of his research areas is studying the possibilities for pharmacological intervention using realistic computer models of pathological network conditions as they occur in schizophrenia or depression. These studies depend on a wealth of data obtained from in vivo, in vitro and anatomical studies, and are continuously validated via experimental predictions. Based on neural models constructed that way, the Durstewitz group investigates which pharmacologically addressable parameter settings could be changed to restore a “healthy” state in the simulated model networks. In a sense, Durstewitz attempts to treat the disease in the simulated mathematical model. This 
new research approach is also called „in silico neuro-pharmacology“, because the discovery process ultimately takes place on silicon chip-based computers. In the future, Durstewitz plans to test the pharmacological cocktails coming out from his simulation studies in collaborations within the Bern-stein Center using in vivo preparations.

A final area of Durstewitz’ research within the Bernstein context is to identify potentially patho-physiological conditions or their antecedents from network dynamics reconstructed from fMRI or EEG measurements. On this basis, he hopes to find new biomarkers, which indicate underlying conditions of disorders even before the full onset of the disease. „The goal is to detect subtle pathological changes as early as possible in order to act preventively on the course of the disease by medication or behavioral therapies.“

The Durstewitz' group

As coordinator of the Bernstein Center Heidelberg-Mann-heim, he particularly likes integrating the different project results within a common theoretical framework, as well as working with students and designing a specific training program for his area of expertise. Since 2011, Daniel Durstewitz has also taken over the Heisenberg Professorship for Theoretical Neuroscience at CIMH. With so much responsibility, the father of two children has not much time left to actively run „lab work“ himself. His research group—half of them being theoretical physicists, and the other half being electrical engineers, biomathematicians, and physiologists—performs 
most of the actual work. However, Durstewitz, who refers to science as his major hobby, cannot do completely 
without directly working on scientific problems himself: „In the evenings after 8 pm, I sit down at my desk and analyze some data on my own, or work on methodological tools.“