Martin Müller

Control of Synaptic Function

Synaptic transmission is a highly conserved process across species that is required for adaptive animal behavior. On the one hand, changes in synaptic transmission are crucial for learning and memory formation. On the other hand, uncontrolled changes in synaptic transmission may result in pathological states such as epilepsy or migraine. It is therefore important to understand how synapse function is controlled.

We are interested in understanding how characteristic functional properties of synapses are established, maintained, and modulated. What are the mechanisms that stabilize synapse function, and how are these mechanisms related to the mechanisms that alter synaptic activity? We study these questions by combining genetic approaches with detailed functional analysis of synaptic transmission at a large synapse of the genetic model organism Drosophila melanogaster. This system allows us to discover new genes and processes involved in controlling synaptic function using forward genetics, electrophysiology, and functional imaging.

A. Presynaptic boutons of a larval Drosophila neuromuscular synapse filled with a Ca2+-sensitive dye. B. Single action-potential stimulation of a wild-type synapse induces a transient elevation of the intracellular free Ca2+ concentration. C. Enhanced presynaptic Ca2+ influx stabilizes synaptic efficacy in response to perturbation of postsynaptic neurotransmitter receptor function (GluRIIA) .

Currently, we are particularly interested in how neurotransmitter release is finely tuned by a homeostatic signaling system that stabilizes synapse function. In a next step, we plan to translate interesting findings from Drosophila into the mammalian nervous system. We hope that this approach may help unraveling the mechanisms that are involved in preventing uncontrolled neural activity during neural pathology, while providing the nervous system with the capacity for change.

CV

2013– SNSF Assistant Professor, IMLS, University of Zurich, Switzerland
2008–2013: Postdoctoral fellow with Grae Davis, University of California, San Francisco, CA, USA
2004–2008: Graduate student with Ralf Schneggenburger, EPFL, Lausanne, Switzerland, and Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
2001–2004: Master Program in Neural and Behavioral Sciences, Graduate School of Neural and Behavioral Sciences, International Max Planck Research School, University of Tübingen, Germany