Abstract
Zinc and copper are involved in neuronal differentiation and synaptic plasticity but the molecular mechanisms behind these processes are still elusive due in part to the difficulty of imaging trace metals at the synapse level. We correlate stimulated emission depletion (STED) microscopy of proteins and synchrotron X-ray fluorescence (SXRF) imaging of trace metals, both performed with 40 nm spatial resolution, on primary rat hippocampal neurons. We achieve a detection limit for trace metals in the zeptogram level per pixel. We reveal the co-localization at the nanoscale of zinc and tubulin in dendrites with a molecular ratio of about one zinc atom per tubulin-αβ dimer. We observe the co-segregation of copper and F-actin within the nano-architecture of dendritic spines. Overall, the combination of STED super-resolution microscopy and SXRF nano-imaging indicates new functions for zinc and copper in the regulation of the synaptic cytoskeleton associated to memory formation.