Variability in the Munc13-1 content of excitatory release sites
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 wi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/67468 |
| _version_ | 1818019492798660608 |
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| author | Maria Rita Karlocai Judit Heredi Tünde Benedek Noemi Holderith Andrea Lorincz Zoltan Nusser |
| author_facet | Maria Rita Karlocai Judit Heredi Tünde Benedek Noemi Holderith Andrea Lorincz Zoltan Nusser |
| author_sort | Maria Rita Karlocai |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:53:11Z |
| format | Article |
| id | doaj.art-b31ff5c1b7a741258b1b57c49d08a87b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:53:11Z |
| publishDate | 2021-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b31ff5c1b7a741258b1b57c49d08a87b2022-12-22T02:05:08ZengeLife Sciences Publications LtdeLife2050-084X2021-04-011010.7554/eLife.67468Variability in the Munc13-1 content of excitatory release sitesMaria Rita Karlocai0Judit Heredi1Tünde Benedek2Noemi Holderith3https://orcid.org/0000-0002-0024-3980Andrea Lorincz4https://orcid.org/0000-0003-2430-5290Zoltan Nusser5https://orcid.org/0000-0001-7004-4111Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Budapest, HungaryLaboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Budapest, HungaryLaboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Budapest, HungaryLaboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Budapest, HungaryLaboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Budapest, HungaryLaboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Budapest, HungaryThe 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.https://elifesciences.org/articles/67468synaptic transmissionpatch clamphippocampus |
| spellingShingle | Maria Rita Karlocai Judit Heredi Tünde Benedek Noemi Holderith Andrea Lorincz Zoltan Nusser Variability in the Munc13-1 content of excitatory release sites eLife synaptic transmission patch clamp hippocampus |
| title | Variability in the Munc13-1 content of excitatory release sites |
| title_full | Variability in the Munc13-1 content of excitatory release sites |
| title_fullStr | Variability in the Munc13-1 content of excitatory release sites |
| title_full_unstemmed | Variability in the Munc13-1 content of excitatory release sites |
| title_short | Variability in the Munc13-1 content of excitatory release sites |
| title_sort | variability in the munc13 1 content of excitatory release sites |
| topic | synaptic transmission patch clamp hippocampus |
| url | https://elifesciences.org/articles/67468 |
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