Structure and plasticity of silent synapses in developing hippocampal neurons visualized by super-resolution imaging

Abstract

AbstractExcitatory synapses in the mammalian brain exhibit diverse functional properties in transmission and plasticity. Directly visualizing the structural correlates of such functional heterogeneity is often hindered by the diffraction-limited resolution of conventional optical imaging techniques. Here, we used super-resolution stochastic optical reconstruction microscopy (STORM) to resolve structurally distinct excitatory synapses formed on dendritic shafts and spines. The majority of these shaft synapses contained N-methyl-d-aspartate receptors (NMDARs) but not α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), suggesting that they were functionally silent. During development, as more spine synapses formed with increasing sizes and expression of AMPARs and NMDARs, shaft synapses exhibited moderate reduction in density with largely unchanged sizes and receptor expression. Furthermore, upon glycine stimulation to induce chemical long-term potentiation (cLTP), the previously silent shaft synapses became functional shaft synapses by recruiting more AMPARs than did spine synapses. Thus, silent shaft synapse may represent a synaptic state in developing neurons with enhanced capacity of activity-dependent potentiation.