Transsynaptic Assemblies Link Domains of Presynaptic and Postsynaptic Intracellular Structures across the Synaptic...

Area of Science:

• Neuroscience
• Cell Biology
• Structural Biology

Background:

• Chemical synapses are crucial for neuronal communication, comprising presynaptic, postsynaptic, and cleft regions.
• Super-resolution microscopy and cryo-electron tomography suggest molecular alignment across the synaptic cleft, forming transsynaptic assemblies.
• The precise structure and connectivity of these transsynaptic assemblies remain incompletely understood.

Purpose of the Study:

• To characterize the composition, distribution, and interactions of all transsynaptic assemblies in excitatory and inhibitory synapses.
• To provide a detailed three-dimensional structural basis for transsynaptic alignment and molecular organization.
• To investigate how transsynaptic assemblies relate to synaptic vesicles and postsynaptic density scaffolding.

Main Methods:

• High-pressure freezing and freeze-substitution of dissociated rat hippocampal neuronal cultures.
• Cryo-electron tomography to generate high-resolution three-dimensional renderings of synaptic structures.
• Analysis of connectivity between cleft-spanning structures and intracellular components in both compartments.

Main Results:

• The majority of transsynaptic structures connect to both presynaptic and postsynaptic compartments.
• Transsynaptic assemblies frequently link synaptic vesicles and postsynaptic density scaffolding.
• Assemblies exhibit complex entanglement, sharing intracellular components and forming larger functional domains around vesicle clusters.

Conclusions:

• Transsynaptic assemblies physically connect and coordinate molecular organization across the entire synapse.
• These assemblies provide a structural foundation for the synapse-spanning nanocolumns observed with light microscopy.
• The interconnected nature of assemblies suggests specialized functional domains within the synapse.