Cited by 37Neuroscience and Neuropharmacology ResearchCellular transport and secretionGenetics and Neurodevelopmental Disorders

Variability in the Munc13-1 content of excitatory release sites.

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Karlocai, Maria Rita, Heredi, Judit, Benedek, Tünde, Holderith, Noemi, Lorincz, Andrea, Nusser, Zoltan·2021·eLife

Abstract

The molecular mechanisms underlying the diversity of cortical glutamatergic synapses are still incompletely understood. Here, we tested the hypothesis that presynaptic active zones (AZs) are constructed from molecularly uniform, independent release sites (RSs), the number of which scales linearly with the AZ size. Paired recordings between hippocampal CA1 pyramidal cells and fast-spiking interneurons in acute slices from adult mice followed by quantal analysis demonstrate large variability in the number of RSs ( N ) at these connections. High-resolution molecular analysis of functionally characterized synapses reveals variability in the content of one of the key vesicle priming factors – Munc13-1 – in AZs that possess the same N . Replica immunolabeling also shows a threefold variability in the total Munc13-1 content of AZs of identical size and a fourfold variability in the size and density of Munc13-1 clusters within the AZs. Our results provide evidence for quantitative molecular heterogeneity of RSs and support a model in which the AZ is built up from variable numbers of molecularly heterogeneous, but independent RSs.

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Authors
Karlocai, M. R., Heredi, J., Benedek, T., Holderith, N., Lorincz, A., & Nusser, Z.
Affiliations
  • Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Budapest, Hungary
  • University of Alabama at Birmingham (US)
Venue
eLife
Published
2021-04-27
Volume
10
ISSN
2050-084X (ISSN-L)
OpenAlex
W3157632604
Cited by
37
References
61
Citations by year
2026: 3 · 2025: 6 · 2024: 9 · 2023: 5 · 2022: 13 · 2021: 1
FWCI
3.23
Type
journal article
Language
en
Open access
Locations
  • eLife (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • European Research Council (ERC-AG 787157)
  • National Research Development and Innovation Office (NAP2.0)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
Munc13-1, release sites, active zone, synaptic vesicle priming, glutamatergic synapses, synaptic heterogeneity, CA1 pyramidal neurons, fast-spiking interneurons, quantal analysis, paired recordings, synaptic vesicle release
MeSH terms
Animals, Electrophysiology, Female, Fluorescent Antibody Technique, Freeze Fracturing, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Synapses, Presynaptic Terminals, Mice, CA1 Region, Hippocampal

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