Synapses undergo long-lasting modifications of their structure, function and composition to store information, but the precise evolution of these changes has never been observed in real time.

Here we present the chronological sequence of the protein reorganization that takes place during the early phase of long-term potentiation (LTP), induced in a single dendritic spine by two-photon glutamate uncaging. Using fluorescent and photoactivatable protein fusions we identified three different patterns of protein dynamics: (1) A set of proteins that moves rapidly to the spine in a transient initial phase (1-2 min), including actin and, specially cofilin 1, which gets massively concentrated in the spine. (2) During the stabilization of the spine growth (2-7 min), a second group of proteins, including CaMKII a and ß, the GluR1 subunit of AMPAR, a-actinin 2, Drebrin A and Profilin IIa, gradually translocate to the spine, at different rates, to consolidate the new structure. (3) Surprisingly, the main scaffolding components of the postsynaptic density (PSD), like PSD-95, Homer 1b, Shank 1b and SAP-97, do not change their total amount, spine sub-localization or turn-over during the subsequent 60 min. This suggests a totally independent structural plasticity between the whole spine and its PSD. To confirm it, we visualized the fine ultrastructure of a single potentiated spine at different moments of LTP induction, by combining two-photon uncaging, imaging and photo-localization with electron microscopy.

These results provide a broad view with high spatial and temporal resolution of the structural and molecular changes that underlie synaptic plasticity in individual spines.

Society for Neuroscience Abstract, 2009.