Research Interests

The Rosenmund lab examines the molecular mechanisms underlying synaptic transmission of central synapses.

Within the presynaptic terminal, release of neurotransmitter-filled vesicles is restricted to active zones. In a series of functional highly coordinated and regulated steps synaptic vesicles are filled with neurotransmitter, tether to specific release sites at the active zone, prime to reach fusion competence, and finally fuse in a calcium-triggered event with the plasma membrane to release the neurotransmitter into the synaptic cleft. This chemical signal is than recognized and transduced into an electrical signal by activation of specific receptors at the postsynaptic site.

Elucidation of the mechanisms of synaptic transmission and its regulation is central to the understanding of brain function and dysfunction. Our goal is to quantify and kinetically resolve individual steps within this vesicle cycle. We want to understand which presynaptic proteins; protein-domains and individual residues mediate these steps. Furthermore, we want to identify molecules and mechanisms contributing to heterogeneity in synaptic function. Finally, we want to know how changes of synaptic function such as release probability or short-term plasticity affects the behavior of neurons within defined neuronal networks.

To understand the underlying complexity, an integrative approach including biochemistry, genetics, structural and functional analysis is required. In our lab, we examine synaptic transmission with standard patch-clamp electrophysiology and imaging techniques using cultured primary neurons and slices. We functionally characterize synaptic properties of genetic modified mice that bear deletions of- or carry mutations within presynaptic proteins. We also use knock-out mice lacking specific presynaptic proteins to examine protein-domain and -residue functions by gain-of-function rescue experiments using viral overexpression of wild type and mutant proteins.