Our general objective is to close the knowledge gap between nanoscale neuronal morphology and postsynaptic integration of synaptic potentials within a relevant behavioral context using an array of cutting-edge experimental techniques and mathematical modeling. Our approach will overcome the technical bottlenecks that impeded the measurement of rapid voltage signals inside small compartments and visualization of neuronal morphology with sufficiently high spatial resolution in live tissue. The consortium brings together research teams with strong and complementary expertise in STED microscopy and synaptic plasticity (Partner 1: Nägerl), dendritic integration and voltage-sensitive dye (VSD) imaging (Partner 2: DiGregorio), in vivo electrophysiology of hippocampal neurons (Partner 2: Schmidt-Hieber), and biophysical modeling and numerical simulations (Partner 3: Cattaert), using acute slices and intact brains in vivo as experimental preparations. Our overarching hypothesis is that nanoscale features of neuronal morphology (like spine necks and dendritic constrictions) and their spatial distribution in the dendritic tree exert a powerful influence on postsynaptic electrical signalling, shaping postsynaptic potentials in the spine head and their dendritic integration, which ultimately influence the neuronal representations of space. While this hypothesis can be deduced from biophysical theory, the lack of experimental determination of key biophysical parameters (like spine neck resistances) limits the relevance of models alone. Therefore, it is important to overcome the technical limitations of micro-compartment voltage recordings, in order to directly and faithfully assess electrical signalling in spines and their parent dendrites.