Presynapses contain distinct actin nanostructures

Area of Science:

• Neuroscience
• Cell Biology
• Cytoskeleton Dynamics

Background:

• The precise role and architecture of the actin cytoskeleton at presynapses are not well understood.
• This knowledge gap limits our comprehension of synaptic physiology and neurotransmission.

Purpose of the Study:

• To visualize and characterize the architecture of presynaptic actin.
• To investigate the functional impact of actin enrichment on presynaptic components and synaptic vesicle cycling.

Main Methods:

• Utilized diffraction-limited and super-resolution microscopy on a validated model of bead-induced presynapses.
• Employed Single Molecule Localization Microscopy (SMLM) to resolve actin nanostructures.
• Used CRISPR-tagging of endogenous actin in cultured neurons for validation.

Main Results:

• Identified actin-enriched presynapses with higher concentrations of presynaptic components and increased synaptic vesicle cycling.
• Defined three distinct presynaptic actin nanostructures: an active zone mesh, actin rails, and actin corrals.
• Demonstrated an optimal actin amount for presynaptic function and identified distinct actin structures.

Conclusions:

• Presynaptic actin architecture is diverse, featuring specific nanostructures that influence synaptic function.
• Actin enrichment plays a significant role in organizing presynaptic components and regulating synaptic vesicle dynamics.
• These findings provide new insights into the structural basis of synaptic transmission and plasticity.