SYNAPTIC NANO-ARCHIECTURE

Experience and neuronal activity induce long-lasting changes in dendritic spine shape and size, which are thought to be a structural correlate of learning and memory. We are using use super-resolution microscopy examine how pre- and post-synaptic proteins are organized. We have found that they have a surprising, almost digital organization. Pre- and post-synaptic proteins form discrete and aligned nanomodules of synaptic proteins whose number scales linearly with spine size. NMDA-type glutamate receptor-mediated increases in spine size are accompanied both by enhanced mobility of pre- and post-synaptic modules which remained aligned with each other —suggesting trans-synaptic interactions that are maintained during structural plasticity — and by the coordinated addition of new nanomodules, suggesting an architectural basis for spine expansion.

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​The movie shows STED imaging of pre- (green) and post-synaptic (red) proteins. In control and non-responsive spines that do not change in size, there is little movement. However, in potentiated spines (middle) nanomodules move more. In addition, as the spine size increases the spine gets more nanomodules. Movie from Hruska et al., Nature Neuroscience, 2018