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Séminaire impromptu - Martin Fuhrmann & Frank Kirchhoff,Role of inhibition in mouse models of AD / Linking the oligodendrocyte lineage with neuronal network activity and vice versa /

Abstract :

Areas of investigation/research focus / Dr. Martin Fuhrman


 Alzheimer’s disease is characterized by two hallmarks, extracellular Ab-deposition and intracellular aggregation of hyperphosphorylated tau. Furthermore, synapse and neuron loss correlates well with cognitive decline. Sterile inflammation carried out by microglia that are part of the innate immune system in the brain, are in the focus of current research. We try to understand how these components contribute to learning and memory deficits under AD-like conditions. On the one hand, we investigate the hypothesis that an imbalance of excitation and inhibition related to synapse and neuron dysfunction contributes to neuronal network disturbance. In this direction we investigate how structural and functional deficits of GABAergic neurons in the hippocampus contribute to learning and memory deficits. On the other hand, we investigate how microglia contribute to synaptic and neuronal deficits. Especially, we are interested in the interaction of microglia with individual synapses and neurons and how that impacts on the integrity neuronal network connectivity. To address these questions we use state of the art in vivo imaging techniques and combine them with electrophysiological, histological and biochemical techniques in transgenic mice. Moreover, we use optogenetics and chemogenetics to specifically activate or inactivated neuronal subsets.

 

Areas of investigation/research focus / Frank Kirchhoff / Molecular Physiology

 Our research focuses on the molecular and cellular mechanisms of neuron-glia interaction in the central nervous system.
We are pursuing two main research questions:
How do glial transmitter receptors sense and modulate synaptic transmission? What is the impact for living organisms?
How do glial cells respond to acute injuries within the central nervous system?

For functional analysis we generated (and are still continuing to develop) transgenic mouse models with cell-type specific expression of various fluorescent proteins (FPs) and inducible gene deletion. We are applying a combination of biochemical and molecular biological methods together with imaging techniques such as two-photon laser-scanning microscopy (2P-LSM) or CCD imaging.