Our research team investigates the coordinated release of neuromodulators via centralized brain-wide axonal networks, and how they fine-tune cognitive functions ranging from attention and flexibility to reward and pleasure. Complex tasks like mustering the necessary motivation to tackle an unpleasant challenge are also controlled by the interplay of neuromodulators in our brain. In our daily lives, however, we constantly encounter deviations from the optimal operation of those networks. Low levels of attention, on the one hand, make it difficult to learn new information, while hyper-attentiveness or low flexibility, on the other end of the spectrum, make it hard to find new solutions.
We conduct our research on a systems-level to understand the properties of these networks: Their basic properties are defined by cellular structures, but when investigating their interplay and functionality our approach has to transcend to a macroscopic level. Our aim is to understand their brain-wide properties and how they are linked to cognitive performance. We are particularly interested to understand how deviations from a normal mode of operation can give rise to mental disorders such as attention deficit, learning disabilities, or even depression. In addition, we know that neuromodulatory networks are impaired in the early stages of neurodegenerative diseases such as Parkinson's or Alzheimer’s disease.
Our systems-level approach often raises novel questions requiring new technologies and tools to answer them. Therefore, our research team combines basic research with tool design and aims to translate our current scientific understanding to new circuit-based stimulation technologies.
To compare and identify features between different neuromodulatory networks, we use viral approaches to precisely perturbate molecular or functional aspects within these networks, in order to be able to link them to behavioral and cognitive changes within an organism. Our methodological portfolio spans different scales: From molecular histology and RNAscope on a cellular level, to in vitro electrophysiology and two-photon imaging of calcium and voltage indicators in acute slices all the way to optical and electrical recordings in freely and head-fixed behaving mice.
We are continuously designing new genetically-encoded tools helping us disentangle organizational principles of neuromodulatory networks in the entire brain. We re-purpose the function of various photoreceptors and luminescent proteins from all animal kingdoms to control and visualize functional aspects of single neurons. We use molecular biology to create these new tools, prepare adeno-associated viruses and test their functionality in cell culture.
We believe that classical pharmacology does not have sufficient spatial and temporal resolution for translating our new insights about these networks into therapies. Therefore, we are working on pre-clinical technologies to non-invasively manipulate and control specific branches of these networks, using optical technologies or electrical transdermal nerve stimulation to tease out specific responses.
Mouse received optogenetic stimulation on one object
to boost memory.
We are thankful for the financial support to our research from many different funding agencies!