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Ultrastructural analysis of wild-type and RIM1α knockout active zones in a large cortical synapse
Katharina Lichter1, Mila Marie Paul2, Martin Pauli3
1Department of Neurosurgery, University Hospital of Würzburg, 97080 Würzburg, Germany; Institute for Physiology, Department of Neurophysiology, Julius-Maximilians-University Würzburg, 97070 Würzburg, Germany; Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, 97080 Würzburg, Germany.
Rab3A-interacting molecule 1α (RIM1α) is vital for synaptic vesicle docking and organization at active zones. Its absence disrupts hippocampal mossy fiber bouton architecture, impacting vesicle release.
Area of Science:
- Neuroscience
- Cell Biology
- Structural Biology
Background:
- Rab3A-interacting molecule (RIM) proteins are essential regulators of fast calcium-triggered synaptic vesicle release at presynaptic active zones (AZs).
- RIM1α specifically plays a role in organizing the presynaptic AZ and tethering synaptic vesicles (SVs) for release.
Purpose of the Study:
- To investigate the role of RIM1α in the 3D architecture of hippocampal giant mossy fiber bouton (MFB) active zones.
- To elucidate how the absence of RIM1α affects synaptic vesicle docking and AZ organization.
Main Methods:
- Utilized 3D electron tomography on rapid cryo-immobilized acute brain slices from RIM1α knockout and wild-type mice.
- Analyzed the structural parameters of active zones and synaptic vesicle distribution.
Main Results:
- RIM1α knockout mice exhibited larger AZs with wider synaptic clefts.
- A significant reduction (3-fold) in tightly docked SVs was observed in RIM1α knockout mice.
- The distance of docked SVs to the AZ center increased, and the electron-dense material width decreased, indicating altered AZ structure and vesicle pool heterogeneity.
Conclusions:
- RIM1α is crucial for maintaining normal synaptic architecture and vesicle pool organization in hippocampal MFBs.
- Beyond its role in tight SV docking, RIM1α is indispensable for the structural integrity of the active zone.
