Dynamic nanoscale architecture of synaptic vesicle fusion in mouse hippocampal neurons.

ABSTRACT: Synaptic vesicle (SV) fusion is not only tightly coordinated but also happens at a millisecond timescale. Competing models for fusion initiation and propagation suggest tight docking and hemifusion of SVs or localized lipid rearrangements leading to tip-like membrane contacts. Yet, a direct nanoscale examination of the full SV fusion sequence has been lacking. Here, we establish a workflow for timed in situ cryo-electron tomography of optogenetically stimulated mouse neurons to capture the complete SV fusion sequence - from SV recruitment to fusion pore formation, opening and collapse - with near-native structural preservation. Notably, tethered SVs directly undergo fusion initiation via stalk formation, without preceding tight docking or SV flattening. The plasma membrane forms a minimal

SUBMITTER: Kroll J 

PROVIDER: S-EPMC12706093 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature