NIH Research Festival
The synapse is a complex ballet with the players, their roles, and their associations largely hidden by scale. To understand the synapse, the composition and distribution of components in each compartment has largely been analyzed and contextualized separately. Recently, advances in 3D light and electron microscopy techniques have revealed coordination between the presynaptic, postsynaptic, and cleft compartments. It is now clear that certain proteins align across the synapse and within the cleft. Here, 3D renderings visualize electron dense material from electron tomographic reconstructions of high-pressure frozen and freeze-substituted dissociated hippocampal rat neuronal cultures. In these renderings, nearly all cleft-spanning structures connect with a structure in either the pre- or postsynaptic compartment. More than half of all the abundant cleft-spanning structures connect to intracellular structures in both. These full transsynaptic assemblies can link with one another through shared intracellular structures. The resulting large clusters of intracellular structures grouped by linked transsynaptic assemblies are common around vesicles near the active zone membrane and align with groups of large structures with scaffolding morphology in the postsynaptic compartment. Here, we enumerate different types of assemblies, describe their associations, and map their distribution within the synapse. In our interpretation, the intracellular portion of linked assemblies form domains. The cleft components physically link these pre- and postsynaptic domains into nanocolumns. The mechanical forces underpinning this alignment may influence synaptic functions like endo- and exocytosis.
Scientific Focus Area: Neuroscience
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