Ultrastructural analysis of wild-type and RIM1α knockout active zones in a large cortical synapse

Katharina Lichter; Mila Marie Paul; Martin Pauli; Susanne Schoch; Philip Kollmannsberger; Christian Stigloher; Manfred Heckmann; Anna-Leena Sirén

doi:10.1016/j.celrep.2022.111382

Ultrastructural analysis of wild-type and RIM1α knockout active zones in a large cortical synapse

Cell Rep. 2022 Sep 20;40(12):111382. doi: 10.1016/j.celrep.2022.111382.

Authors

Katharina Lichter¹, Mila Marie Paul², Martin Pauli³, Susanne Schoch⁴, Philip Kollmannsberger⁵, Christian Stigloher⁶, Manfred Heckmann⁷, Anna-Leena Sirén⁸

Affiliations

¹ Department 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.
² Institute for Physiology, Department of Neurophysiology, Julius-Maximilians-University Würzburg, 97070 Würzburg, Germany; Department of Orthopedic Trauma, Hand, Plastic and Reconstructive Surgery, University Hospital of Würzburg, 97080 Würzburg, Germany.
³ Institute for Physiology, Department of Neurophysiology, Julius-Maximilians-University Würzburg, 97070 Würzburg, Germany.
⁴ Department of Neuropathology and Department of Epileptology, University Hospital Bonn, 53127 Bonn, Germany.
⁵ Center for Computational and Theoretical Biology, Julius-Maximilians-University Würzburg, 97074 Würzburg, Germany.
⁶ Imaging Core Facility, Biocenter, University of Würzburg, 97074 Würzburg, Germany. Electronic address: [email protected].
⁷ Institute for Physiology, Department of Neurophysiology, Julius-Maximilians-University Würzburg, 97070 Würzburg, Germany. Electronic address: [email protected].
⁸ Department of Neurosurgery, University Hospital of Würzburg, 97080 Würzburg, Germany; Institute for Physiology, Department of Neurophysiology, Julius-Maximilians-University Würzburg, 97070 Würzburg, Germany. Electronic address: [email protected].

PMID: 36130490
DOI: 10.1016/j.celrep.2022.111382

Abstract

Rab3A-interacting molecule (RIM) is crucial for fast Ca²⁺-triggered synaptic vesicle (SV) release in presynaptic 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 RIM1α^-/- and wild-type mice. In RIM1α^-/-, 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 RIM1α^-/- is more heterogeneous. Thus, RIM1α, besides its role in tight SV docking, is crucial for synaptic architecture and vesicle pool organization in MFBs.

Keywords: CA3; CP: Neuroscience; RIM1α; SV pool; active zone; acute brain slices; electron tomography; high-pressure freezing; hippocampal mossy fiber bouton; synaptic ultrastructure, presynaptic.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Mice
Mossy Fibers, Hippocampal / ultrastructure
Presynaptic Terminals / ultrastructure
Synapses* / ultrastructure
Synaptic Transmission
Synaptic Vesicles* / ultrastructure