Characterization of the function of vascular pathways in nervous system development and plasticity

We aim to delineate the molecular pathways that govern the communication between the neuronal and vascular systems to understand fundamental mechanisms of brain development, function, and dysfunction. Using state-of-the-art inducible and cell type-specific mouse genetics, in combination with high-resolution light microscopy, multi-photon live imaging, and cutting-edge electrophysiology, we explore the contribution of vascular signaling to building proper vascular/neuronal/glial interaction and functional neuronal networks.

Characterization of key signaling pathways regulating the blood-brain barrier

One of the main functions of the neurovascular unit is to preserve a selective transport between the blood and the brain parenchyma. The blood-brain barrier designates this restricted passage of substances through the brain endothelium.

In our lab, we are studying which molecular pathways are involved in the generation and maintenance of the CNS barriers in physiological and disease-associated conditions. For this purpose, we use mouse genetics, injection of tracers, and advanced confocal imaging. We have also established several collaborations to study the barrier integrity by electron microscopy.

Identifying novel roles for neuronal pathways influencing angiogenesis

The nervous and the vascular system share the same molecular vocabulary. We have contributed to show that classical neuronal cues also modulate the vascularization of the central nervous system (CNS). These molecules with a dual role in both systems are named angioneurins.

In this research project, we explore the signaling mechanisms of new angioneurins acting as vascular regulators during CNS development as well as in response to tissue damage.

Instructive roles of the vasculature on the neuronal organization in the embryonic and adult zebrafish

We are interested in elucidating the molecular pathways involved in the crosstalk between vascular and nervous systems and how this crosstalk signaling is integrated among the different cellular players (neurons, endothelial cells, glial cells) during the development and homeostasis of zebrafish trunk and brain.

We use state-of-the-art genetic approaches and fluorescent transgenic lines for in vivo imaging to explore the interface between the neuronal and vascular system during development as well as tissue damage.

Study of endothelial cell heterogeneity in the CNS

Using up-to-date transcriptomic approaches, we investigate the characteristics of different subtypes of endothelial cells in the brain and how the neurovascular interface modulates their molecular signature in different physiological and pathological scenarios.

Molecular mechanisms regulating homeostatic changes at dendritic arbors and dendritic spines

Structural plasticity is a fundamental process accompanying both Hebbian and homeostatic synaptic plasticity and it is necessary for proper circuit wiring and maintenance.

We are investigating the regulatory mechanisms that correlate glutamate receptor dynamics and spine morphology during synaptic plasticity. To this aim, we use mouse genetics, neuronal and organotypic cultures, state-of-the-art confocal and multiphoton imaging as well as expansion microscopy. Changes in synaptic plasticity are quantitatively assessed with electrophysiological approaches such as patch-clamp or multi-electrode array.

These research projects led by Herbert Zimmermann comprised two major fields: The functional and biochemical characterization of synaptic vesicles and intercellular signaling via extracellular nucleotides in the nervous system.

The study of synaptic vesicles began with a detailed analysis of the synaptic vesicle life cycle under conditions of stimulation and rest and culminated in the analysis of the vesicular and synaptosomal proteome, including the identification and characterization of novel synaptic vesicle proteins.

Nucleotides such as ATP, ADP, UTP or UDP are released from cells and exert their function via specific receptors that are either ion channels or G-protein-coupled. Particular emphasis was placed on the cell biology and biochemistry of ectonucleotidases, nucleotide-hydrolyzing enzymes that terminate or modulate the function of extracellular nucleotides. A recent development concerned the role of extracellular nucleotides and ectonucleotidases in the control of neurogenesis, the formation of new nerve cells in the adult nervous system, as well as the development of specific ectonucleotidase inhibitors.

The research project is currently not active.