Prof. David P. Wolfer, MD
Our research aims at better understanding of the biological basis of cognitive function in the normal and diseased brain. We work with animal models, combining the analysis of behavior with functional and comparative neuroanatomy, stereotactic lesions, EEG-recordings, pharmacology, and – in collaboration with other labs – molecular genetic approaches. We also investigate the influence of genetic variation, age, environment and life style on cognitive function and the underlying brain circuitry.
I am particularly interested in improving the analysis of mouse behavior. Thanks to the rapid development of molecular genetics, mouse models are now used on a large scale to study molecular and cellular mechanisms of cognitive function and psychiatric diseases. Analysis of behavior is indispensable to fully exploit the potential of these models but is currently facing a number of challenges:
- Current approaches to behavioral phenotyping lack the efficiency and throughput needed to keep pace with the rapidly growing number of mouse models being created.
- There is rising general concern about the reproducibility of research results, and behavioral analysis of mouse models is regarded as one of the most worrisome areas.
- The validity of several mouse models has been questioned due to failure to translate preclinical results into clinical applications.
- Awareness of animal welfare issues is increasing, in particular regarding the adverse consequences of stimulus deprivation and social isolation on the wellbeing of rodents.
In order to address these challenges, we
- Improve the validity of existing behavioral tests by adapting our test battery to specific needs and behavioral repertoire of mice and by extracting more meaningful behavioral parameters.
- Developed the IntelliCage system for automated multidimensional assessment of mouse behavior in a social home cage setting. This increases throughput, optimizes welfare and improves reproducibility by minimizing effects of lab environment and handling by humans.
- Use miniature neurologgers to record EEG in freely behaving and socially interacting mice.
- Design new approaches to data analysis exploiting the free statistical software environment R in order to increase efficiency and reduce observer bias.
Our expertise in neuroanatomy and behavioral phenotyping is the basis for our engagement in several collaborative projects using mouse models related to psychiatric disorders. With the Institute for Pharmacy and Molecular Biotechnology at the University of Heidelberg, we investigate the physiological function of amyloid precursor and related proteins. We collaborate with the UZH Institute of Medical Microbiology to test the hypothesis that inaccurate translation at mitochondrial and cytosolic ribosomes contributes to brain aging. In collaboration with the MPI for Biophysical Chemistry in Göttingen, we investigate a mouse model with a genetic ablation of the hippocampus and most of the neocortex. Finally, together with the RIKEN Brain Science Institute in Japan, we study the function of netrin G1 and G2 which may play a role in the pathogenesis of schizophrenia and autism spectrum disorders.
PD Irmgard Amrein, PhD
Our special interest is to investigate eco-evolutionary adaptations in the structure of the mammalian hippocampus – How do structural specializations relate to the evolutionary history of animals, and how do they translate into behaviors that allow the animals to compete in their ecological niches? In this context, we perform comparative quantitative analysis of functionally defined neuron populations in the hippocampus and adjacent cortical areas, with a special focus on adult-born neurons. Most of the animals studied are wild-living species that show unique environmental adaptations. If feasible, animals are tested behaviorally using the IntelliCage system. We have been able to define anatomical patterns that characterize taxonomic groups, and within these groups, habitat requirements that can shape hippocampal neurogenesis and quantitative relations between hippocampal cell populations - revealing surprising features that cannot be observed in laboratory rodents.