A03
Our mouse-human project aims to study how impairments in inhibitory microcircuits during theta states affect neural processing of environmental inputs, particularly in Alzheimer’s disease models. The research will focus on different types of inhibitory circuit motifs and their impact on cognitive functions such as memory encoding and retrieval. By utilizing hAPP mouse models, researchers will investigate how beta-amyloidosis disrupts these circuits and contributes to memory deficits. We demonstrate to MCI patients how locomotion counteracts cognitive limitations. The study will also explore potential therapeutic targets related to inhibitory neuron function. Overall, this work package aims to uncover key neural mechanisms underlying cognitive impairment in Alzheimer’s disease, with a specific focus on the role of inhibitory circuits during theta states.
Principal Investigators

Dr. Stefan Dürschmid

Prof. Dr. med. Stefan Remy
Co-Workers

Xinyun Che

Felix Kuhn
Our Research
In our experimental approach we use transgenic mice with AD specific hallmarks, such as the accumulation of amyloid beta plaques. We use fluorescence in-situ hybridization of cell type specific mRNA to identify differences in the prevalence and distribution of different molecular cell types between wild type and transgenic animals. With two-photon in vivo calcium imaging we are further able to image the activity of hundreds of neurons in the hippocampus of the animals while they are performing in a spatial memory task. Machine learning based analysis techniques allow us to find correlations between pathological behavior and impaired neuronal activity. We also investigate to which extend the transgenic animals allocate cognitive resources to compensate for the impairment of specific hippocampal circuitries.
Locomotion is known to alter HC activity in rodents. In a translational approach we study whether locomotion has the potential to regulate HC theta activity and leads to improvement of memory capacity in human subjects. The notion that motion and cognition are densely linked dates back to the astonishingly modern Peripatetic school of philosophy in ancient Greece. A central claim is that exercise can improve memory, attention, and help people think creatively. Unfortunately, only a few behavioral studies in humans showed that walking is associated with better performance in divergent thinking. However, the neurophysiological mechanisms at the functional neural network level are still unclear.
The aims of our research
The aim of our research is to investigate whether and how motion can affect the encoding of information into memory and retrieval of memory content and how neural network activity enables this motion and cognition interaction. Utilizing the exquisite temporal and spectral resolution of non-invasive magnetoencephalographic and invasive electrocorticographic recordings we seek to delineate the neuronal mechanisms.
