Ultrastructural analysis of wild-type and RIM1a knockout active zones in a large cortical synapse

Rab3A-interacting molecule (RIM) is crucial for fast Ca2+-triggered synaptic vesicle (SV) release in presynap-tic active zones (AZs). We investigated hippocampal giant mossy fiber bouton (MFB) AZ architecture in 3D using electron tomography of rapid cryo-immobilized acute brain slices in RIM1a-/-and wild-type mice. In RIM1a-/-, AZs are larger with increased synaptic cleft widths and a 3-fold reduced number of tightly docked SVs (0-2 nm). The distance of tightly docked SVs to the AZ center is increased from 110 to 195 nm, and the width of their electron-dense material between outer SV membrane and AZ membrane is reduced. Furthermore, the SV pool in RIM1a-/-is more heterogeneous. Thus, RIM1a, besides its role in tight SV docking, is crucial for synaptic architecture and vesicle pool organization in MFBs.

Automated summary

RIM1a is crucial for the architecture of synaptic vesicles and vesicle pool organization in MFBs. In RIM1a-/-, the size of active zones is larger, the number of tightly docked vesicles is reduced, and the synaptic cleft is wider. Additionally, the organization of the vesicle pool is more heterogeneous.