Unc13A and Unc13B contribute to the decoding of distinct sensory information in Drosophila
Open accessAbstract
The physical distance between presynaptic Ca 2+ channels and the Ca 2+ sensors triggering the release of neurotransmitter-containing vesicles regulates short-term plasticity (STP). While STP is highly diversified across synapse types, the computational and behavioral relevance of this diversity remains unclear. In the Drosophila brain, at nanoscale level, we can distinguish distinct coupling distances between Ca 2+ channels and the (m)unc13 family priming factors, Unc13A and Unc13B. Importantly, coupling distance defines release components with distinct STP characteristics. Here, we show that while Unc13A and Unc13B both contribute to synaptic signalling, they play distinct roles in neural decoding of olfactory information at excitatory projection neuron (ePN) output synapses. Unc13A clusters closer to Ca 2+ channels than Unc13B, specifically promoting fast phasic signal transfer. Reduction of Unc13A in ePNs attenuates responses to both aversive and appetitive stimuli, while reduction of Unc13B provokes a general shift towards appetitive values. Collectively, we provide direct genetic evidence that release components of distinct nanoscopic coupling distances differentially control STP to play distinct roles in neural decoding of sensory information.
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Unc13a expression in mushroom bodies plays a fundamental role in olfactory memory encoding in Drosophila, and hippocampal expression of Lpl is necessary for synaptic vesicle recycling and acquisition of memories in mice.
“Unc13a expression in mushroom bodies plays a fundamental role in olfactory memory encoding in Drosophila [86], and hippocampal expression of lipoprotein lipase (Lpl) is necessary for synaptic vesicle recycling and acquisition of memories in mice [87].”
From Rapid changes in plasma corticosterone and medial amygdala transcriptome profiles during social status change reveal molecular pathways associated with a major life history transition in mouse dominance hierarchies (2025) · cites this paper as [86]
The Results section (‘Unc13A specifically promotes a fast, phasic release component at ePN output synapses’; page unavailable) reports that Unc13A knockdown reduces odor-evoked responses at mushroom-body calyx synapses. It does not show that Unc13A is required for olfactory memory encoding; that finding appears in the title of Woitkuhn et al. (2020) in the References, not as a result of this study. The mouse Lpl clause is attached to a different citation and is not assessed here. (LLM, conf=0.84)
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Milewski, T. M., Lee, W., Young, R. L., Hofmann, H. A., & Curley, J. P. (2025) · PLoS Genetics · doi:10.1371/journal.pgen.1011548 · Cited by 7 · see citing works
- Authors
- Pooryasin, A., Maglione, M., Schubert, M., Matkovic-Rachid, T., Hasheminasab, S.-M., Pech, U., Fiala, A., Mielke, T., & Sigrist, S. J.
- Affiliations
- Freie Universität Berlin (DE)
- NeuroCure Cluster of Excellence (DE)
- German Cancer Research Center (DE)
- University of Göttingen (DE)
- Max Planck Institute for Molecular Genetics (DE)
- Corresponding author
- Sigrist, Stephan J.
- ORCID
- Venue
- Nature Communications
- Published
- 2021-03-26
- Volume
- 12
- Issue
- 1
- Pages
- 1932-1932
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7997984
- OpenAlex
- W3137992524
- Cited by
- 35
- References
- 5
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 6 · 2023: 5 · 2022: 10 · 2021: 4
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Lirias (acceptedVersion, cc-by)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
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- Funders
- Deutsche Forschungsgemeinschaft (SFB 1315)
- Agence Nationale de la Recherche (ANR-17-CE16-0026)
- Freie Universität Berlin
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- UNC13A, short-term plasticity, synaptic vesicle release, Drosophila
- MeSH terms
- Animals, Appetitive Behavior, Calcium, Drosophila melanogaster, Female, Interneurons, Membrane Proteins, Nerve Tissue Proteins, Synaptic Transmission, Neuronal Plasticity, Synapses, Synaptic Vesicles, Calcium Channels, Microscopy, Confocal, Protein Isoforms, Drosophila Proteins, Animals, Genetically Modified, RNA Interference
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