Our research group focuses on delineating the molecular and mechanistic basis of neurotransmitter release in nerve terminals and understanding how it is altered in neurological disorders. Controlled release of neurotransmitters stored in synaptic vesicles (SV) is central to all information processing in the brain. This process relies on efficient coupling of SV fusion to the triggering signal - action potential evoked pre-synaptic calcium influx. During the last three decades, the key proteins that mediate SV exocytosis have been identified. However, the precise molecular mechanisms of calcium-activation of SV exocytosis remain in the center of the debate. Furthermore, mutations in these pre-synaptic proteins that affect neurotransmitter release and SV cycling are linked to a growing number of neurological disorders termed "presynaptic synaptopathies." These include paroxysmal (e.g. epilepsy, migraine, ataxias, dyskinesia), neurodevelopmental and psychiatric disorders.
However, it remains unclear how these mutations cause diseases. We employ multidisciplinary synaptic biochemistry, cell biology, fluorescence imaging, and structural biology tools to develop a quantitative understanding of the molecular mechanisms underlying the timing and the use-dependent plasticity on neurotransmitter release, which is essential for understanding how the brain functions both in health and in disease.