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

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.

• Publication year

  2022

• Venue

  Cell Reports

• Publication date

  2022-09-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.celrep.2022.111382PMID 36130490
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Munc13 structural transitions and oligomers that may choreograph successive stages in vesicle priming for neurotransmitter release

  2022cited by this paper
• The human cognition-enhancing CORD7 mutation increases active zone number and synaptic release.

  2022cited by this paper
• Recruitment of release sites underlies chemical presynaptic potentiation at hippocampal mossy fiber boutons

  2021cited by this paper
• RIM-Binding Protein 2 Organizes Ca2+ Channel Topography and Regulates Release Probability and Vesicle Replenishment at a Fast Central Synapse

  2021cited by this paper
• Synapsins and the Synaptic Vesicle Reserve Pool: Floats or Anchors?

  2021cited by this paper
• Active zone compaction correlates with presynaptic homeostatic potentiation.

  2021cited by this paper
• A Trio of Active Zone Proteins Comprised of RIM-BPs, RIMs, and Munc13s Governs Neurotransmitter Release.

  2020cited by this paper
• Functional Electron Microscopy, ‘‘Flash and Freeze,’’ of Identified Cortical Synapses in Acute Brain Slices

  2020cited by this paper
• Ultrastructural Correlates of Presynaptic Functional Heterogeneity in Hippocampal Synapses

  2020cited by this paper
• Art and Science of the Cellular Mesoscale.

  2020cited by this paper
• Assembly of the presynaptic active zone.

  2020cited by this paper
• Functional Electron Microscopy, “Flash and Freeze,” of Identified Cortical Synapses in Acute Brain Slices

  2020cited by this paper
• Trans-synaptic assemblies link synaptic vesicles and neuroreceptors

  2020cited by this paper
• Array programming with NumPy

  2020cited by this paper
• Synaptic vesicle pools are a major hidden resting metabolic burden of nerve terminals

  2020cited by this paper
• Overexpression of an ALS-associated FUS mutation in C. elegans disrupts NMJ morphology and leads to defective neuromuscular transmission

  2020cited by this paper
• Disentangling the Roles of RIM and Munc13 in Synaptic Vesicle Localization and Neurotransmission

  2020cited by this paper
• Ultrastructural Imaging of Activity-Dependent Synaptic Membrane-Trafficking Events in Cultured Brain Slices

  2020cited by this paper
• Targeted volumetric single-molecule localization microscopy of defined presynaptic structures in brain sections

  2019cited by this paper
• RIM and RIM-BP Form Presynaptic Active-Zone-like Condensates via Phase Separation.

  2019cited by this paper
• α-Neurexins Together with α2δ-1 Auxiliary Subunits Regulate Ca2+ Influx through Cav2.1 Channels

  2018cited by this paper
• Synaptic vesicles transiently dock to refill release sites

  2018cited by this paper
• A liquid phase of synapsin and lipid vesicles

  2018cited by this paper
• RIM C2B Domains Target Presynaptic Active Zone Functions to PIP2-Containing Membranes.

  2018cited by this paper
• Dynamically Primed Synaptic Vesicle States: Key to Understand Synaptic Short-Term Plasticity.

  2018cited by this paper
• Mitochondria at the neuronal presynapse in health and disease

  2018cited by this paper
• Hypothesis – buttressed rings assemble, clamp, and release SNAREpins for synaptic transmission

  2017cited by this paper
• Heterodimerization of Munc13 C2A domain with RIM regulates synaptic vesicle docking and priming

  2017cited by this paper
• The readily releasable pool of synaptic vesicles.

  2017cited by this paper
• Fusion Competent Synaptic Vesicles Persist upon Active Zone Disruption and Loss of Vesicle Docking.

  2016cited by this paper
• ELKS controls the pool of readily releasable vesicles at excitatory synapses through its N-terminal coiled-coil domains

  2016cited by this paper
• A transsynaptic nanocolumn aligns neurotransmitter release to receptors

  2016cited by this paper
• Ultrastructural analysis of adult mouse neocortex comparing aldehyde perfusion with cryo fixation

  2015cited by this paper
• Loose Coupling Between Ca2+ Channels and Release Sensors at a Plastic Hippocampal Synapse

  2014cited by this paper
• Analysis of specificity in immunoelectron microscopy.

  2014cited by this paper
• Cryo–electron tomography reveals a critical role of RIM1α in synaptic vesicle tethering

  2013cited by this paper
• Deconstructing Complexity: Serial Block-Face Electron Microscopic Analysis of the Hippocampal Mossy Fiber Synapse

  2013cited by this paper
• Differential control of learning and anxiety along the dorsoventral axis of the dentate gyrus.

  2013cited by this paper
• Role of RIM1α in short- and long-term synaptic plasticity at cerebellar parallel fibres

  2013cited by this paper
• RIM Controls Homeostatic Plasticity through Modulation of the Readily-Releasable Vesicle Pool

  2012cited by this paper
• Fiji: an open-source platform for biological-image analysis

  2012cited by this paper
• RIM genes differentially contribute to organizing presynaptic release sites

  2012cited by this paper
• Structural plasticity of hippocampal mossy fiber synapses as revealed by high‐pressure freezing

  2012cited by this paper
• Scikit-learn: Machine Learning in Python

  2011cited by this paper
• RIM determines Ca²+ channel density and vesicle docking at the presynaptic active zone.

  2011cited by this paper
• RIM Proteins Tether Ca Channels to Presynaptic Active Zones via a Direct PDZ-Domain Interaction

  2011cited by this paper
• The Presynaptic Dense Projection of the Caenorhabiditis elegans Cholinergic Neuromuscular Junction Localizes Synaptic Vesicles at the Active Zone through SYD-2/Liprin and UNC-10/RIM-Dependent Interactions

  2011cited by this paper
• Statsmodels: Econometric and Statistical Modeling with Python

  2010cited by this paper
• The Mossy Fiber Bouton: the “Common” or the “Unique” Synapse?

  2010cited by this paper
• Synapsin- and Actin-Dependent Frequency Enhancement in Mouse Hippocampal Mossy Fiber Synapses

  2008cited by this paper
• RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+ channels

  2007cited by this paper
• The optimal height of the synaptic cleft

  2007cited by this paper
• Structural Determinants of Transmission at Large Hippocampal Mossy Fiber Synapses

  2007cited by this paper
• Three-Dimensional Architecture of Presynaptic Terminal Cytomatrix

  2007cited by this paper
• Mutation Associated with an Autosomal Dominant Cone-Rod Dystrophy CORD7 Modifies RIM1-Mediated Modulation of Voltage-Dependent Ca2+ Channels

  2007cited by this paper
• Redundant functions of RIM1α and RIM2α in Ca2+‐triggered neurotransmitter release

  2006cited by this paper
• Preservation of C. elegans tissue via high-pressure freezing and freeze-substitution for ultrastructural analysis and immunocytochemistry.

  2006cited by this paper
• Redundant functions of RIM1alpha and RIM2alpha in Ca(2+)-triggered neurotransmitter release.

  2006cited by this paper
• Analysis of synaptic ultrastructure without fixative using high‐pressure freezing and tomography

  2006cited by this paper
• Patch-clamp recording from mossy fiber terminals in hippocampal slices

  2006cited by this paper
• Long-term rearrangements of hippocampal mossy fiber terminal connectivity in the adult regulated by experience.

  2006cited by this paper
• Binding to Rab3A-interacting Molecule RIM Regulates the Presynaptic Recruitment of Munc13-1 and ubMunc13-2*

  2006cited by this paper
• Automated electron microscope tomography using robust prediction of specimen movements.

  2005cited by this paper
• The presynaptic active zone protein RIM1alpha is critical for normal learning and memory.

  2004cited by this paper
• The Structural Organization of the Readily Releasable Pool of Synaptic Vesicles

  2004cited by this paper
• Quantal transmission at mossy fibre targets in the CA3 region of the rat hippocampus

  2004cited by this paper
• A large pool of releasable vesicles in a cortical glutamatergic synapse

  2003cited by this paper
• RIM1alpha is required for presynaptic long-term potentiation.

  2002cited by this paper
• A family of RIM-binding proteins regulated by alternative splicing: Implications for the genesis of synaptic active zones

  2002cited by this paper
• Single granule cells reliably discharge targets in the hippocampal CA3 network in vivo

  2002cited by this paper
• RIM1α forms a protein scaffold for regulating neurotransmitter release at the active zone

  2002cited by this paper
• RIM1α is required for presynaptic long-term potentiation

  2002cited by this paper
• RIM binding proteins (RBPs) couple Rab3-interacting molecules (RIMs) to voltage-gated Ca(2+) channels.

  2002cited by this paper
• The architecture of active zone material at the frog's neuromuscular junction

  2001cited by this paper
• Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion

  1997cited by this paper
• Computer visualization of three-dimensional image data using IMOD.

  1996cited by this paper
• Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus.

  1993cited by this paper
• Variations in electrophysiological properties of hippocampal neurons in different subfields.

  1982cited by this paper
• Development of the mossy fibers of the dentate gyrus: I. A light and electron microscopic study of the mossy fibers and their expansions

  1981cited by this paper
• THE USE OF LEAD CITRATE AT HIGH pH AS AN ELECTRON-OPAQUE STAIN IN ELECTRON MICROSCOPY

  1963cited by this paper
• Electron Microscopy of Synaptic Contacts on Dendrite Spines of the Cerebral Cortex

  1959cited by this paper

• The flexible synapse - how mossy fiber architecture adapts to changing needs.

  2026cites this paper
• Morphofunctional Features of Hippocampal Mossy Fibers

  2025cites this paper
• Kiss, shrink, run.

  2025cites this paper
• Gene-Environment Interaction of Rims1 and Adolescent Social Isolation on Schizophrenia-Like Behaviors in Mice.

  2025cites this paper
• "Kiss-shrink-run" unifies mechanisms for synaptic vesicle exocytosis and hyperfast recycling.

  2025cites this paper
• Direct evidence for ultrastructures of the α-synuclein-associated synaptic vesicle pool in presynaptic terminals.

  2024cites this paper
• Structure, biophysics, and circuit function of a “giant” cortical presynaptic terminal

  2024cites this paper
• A Reduction in the Readily Releasable Vesicle Pool Impairs GABAergic Inhibition in the Hippocampus after Blood–Brain Barrier Dysfunction

  2024cites this paper
• Short term plasticity at hippocampal mossy fiber synapses.

  2024cites this paper
• Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons

  2023cites this paper
• Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress

  2023cites this paper
• Single-Molecule Localization Microscopy of Presynaptic Active Zones in Drosophila melanogaster after Rapid Cryofixation

  2023cites this paper
• Visualizing Presynaptic Active Zones and Synaptic Vesicles

  2022cites this paper