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Release probability of hippocampal glutamatergic terminals scales with the size of the active zone
Open accessAbstract
Cortical synapses have structural, molecular and functional heterogeneity; our knowledge regarding the relationship between their ultrastructural and functional parameters is still fragmented. Here we asked how the neurotransmitter release probability and presynaptic [Ca(2+)] transients relate to the ultrastructure of rat hippocampal glutamatergic axon terminals. Two-photon Ca(2+) imaging-derived optical quantal analysis and correlated electron microscopic reconstructions revealed a tight correlation between the release probability and the active-zone area. Peak amplitude of [Ca(2+)] transients in single boutons also positively correlated with the active-zone area. Freeze-fracture immunogold labeling revealed that the voltage-gated calcium channel subunit Cav2.1 and the presynaptic protein Rim1/2 are confined to the active zone and their numbers scale linearly with the active-zone area. Gold particles labeling Cav2.1 were nonrandomly distributed in the active zones. Our results demonstrate that the numbers of several active-zone proteins, including presynaptic calcium channels, as well as the number of docked vesicles and the release probability, scale linearly with the active-zone area.
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“However, observations in small CNS synapses of both clustered24,25 and random distribution of Ca2+ channels26, and emerging evidence for channel mobility as an equalizer of Pr for vesicles independent of channel positioning27 suggest that their precise distribution may not be the sole determinant of the AZ release likelihood landscape.”
From A trans-synaptic nanocolumn aligns neurotransmitter release to receptors (2016) · cites this paper as [24]
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“Thus, the number of fusion events must be correlated with the size of presynaptic terminals61 for successful exo-endocytosis coupling.”
From Membrane compression by synaptic vesicle exocytosis triggers ultrafast endocytosis (2023) · cites this paper as [61]
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Krout, M., Oh, K. H., Xiong, A., Frankel, E. B., Kurshan, P. T., Kim, H., & Richmond, J. E. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2220856120 · Cited by 5
Fenrich, K. K., Zhao, E. Y., Wei, Y., Garg, A., & Rose, P. K. (2014) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2014.01.011 · Cited by 5
Orduz, D., Boom, A., Gall, D., Brion, J., Schiffmann, S. N., & Schwaller, B. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00364 · Cited by 6
Holderith, N. B., Lőrincz, A., Katona, G., Rózsa, B. J., Kulik, Á., Watanabe, M., & Nusser, Z. (2015) · Nature Neuroscience · doi:10.1038/nn0116-172 · Cited by 5
Self-citation
Metadata
- Authors
- Holderith, N., Lorincz, A., Katona, G., Rózsa, B., Kulik, A., Watanabe, M., & Nusser, Z.
- Affiliations
- HUN-REN Institute of Experimental Medicine (HU)
- Hokkaido University (JP)
- Venue
- Nature Neuroscience
- Published
- 2012-06-10
- Volume
- 15
- Issue
- 7
- Pages
- 988-997
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3386897
- OpenAlex
- W2093514926
- Cited by
- 405
- References
- 56
- Citations by year
- 2026: 3 · 2025: 15 · 2024: 29 · 2023: 29 · 2022: 30 · 2021: 32 · 2020: 38 · 2019: 28 · 2018: 39 · 2017: 24 · 2016: 30 · 2015: 36 · 2014: 34 · 2013: 32 · 2012: 6
- FWCI
- 14.24
- Type
- journal article
- Language
- en
- Update notices
- erratum (2015-12-29)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust (083484, 090197, 094513, 083484/Z/07/Z, 090197/Z/09/Z, 094513/Z/10/Z)
- 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 › Molecular Biology › Ion channel regulation and function
- Keywords
- release probability, active zone, glutamatergic synapses, CA3 pyramidal cells, voltage-gated calcium channels, Cav2.1, docked vesicles, synaptic ultrastructure, two-photon calcium imaging
- MeSH terms
- Action Potentials, Animals, Hippocampus, Male, Random Allocation, Synaptic Vesicles, Rats, Wistar, Presynaptic Terminals, Calcium Channels, N-Type, Rats
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