Prof. Dr. Stefan Hallermann research on molecular mechanisms of presynaptic plasticity got awarded an ERC Consolidator Grant worth 1.6 million Euros. The goal of this project is to reveal the molecular and biophysical mechanisms of presynaptic plasticity in the vertebrate brain. Building on the strong track record in presynaptic research, Prof. Hallermann group made a technical breakthrough by establishing patch-clamp recordings from small nerve terminals of cultured neocortical neurons with unprecedented high resolution. In addition, they use an innovative super-resolution-microscopy approach resolving the rearrangement of proteins within the presynaptic neurotransmitter release site, which allows high-throughput screening of all major classes of synaptic genes for their involvement in presynaptic plasticity. To reveal the neuron- and plasticity-type specificity, the identified molecular pathways will be analysed in different types of neurons in culture and acute brain slices. Furthermore, the hypothesis that metabolic constraints regulate presynaptic plasticity and that the amyloid pathology of Alzheimer’s disease impacts presynaptic plasticity will be tested. Thus, for the first time in the history of neuroscience, neocortical nerve terminals can be investigated with direct electrophysiological recordings and super-resolution microscopy providing unprecedented spatial and temporal resolution for the analysis of presynaptic plasticity. The results could pave the way for new approaches treating neurological diseases.