Variability in the Munc13-1 content of excitatory release site
- Institute of Experimental Medicine, Hungary
Abstract
The molecular mechanisms underlying the diversity of cortical glutamatergic synapses is 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 3-fold variability in the total Munc13-1 content of AZs of identical size, and a 4-fold 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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Funding
European Research Council (ERC-AG 787157)
- Zoltan Nusser
Hungarian National Brain Research grant
- Zoltan Nusser
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All the experiments were carried out according to the regulations of the Hungarian Act of Animal Care and Experimentation 40/2013 (II.14) and were reviewed and approved by the Animal Committee of the Institute of Experimental Medicine, Budapest.
Copyright
© 2021, Karlocai et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Variability in the Munc13-1 content of excitatory release site
eLife 10:e67468.
https://doi.org/10.7554/eLife.67468
