Presynaptic filopodia form kinapses and promote convective membrane flow to sustain synchronous neurotransmitter release

Synaptic plasticity is the principal mechanism by which neural circuits compute and adapt. Presynaptic plasticity is traditionally regarded as a transient adaptation of the synaptic vesicle fusion and recycling machinery, whereas the role of structural remodeling of synaptic boutons remains unclear. Here, we demonstrate a mechanical coupling between presynaptic structural remodeling and synaptic efficacy. We find that dynamic presynaptic filopodia emerge during active synaptic transmission and deform synaptic boutons while forming transient contacts with postsynaptic structures, which we term neuronal kinapses. Filopodia formation is activity dependent and occurs in intact circuits and human brain. Mechanistically, filopodial growth induces convective in-plane membrane flow toward the filopodium, accelerating release site clearance, a process associated with sustained release probability during repeated synaptic vesicle fusion. As a result, filopodia formation favors an increase in synchronous over asynchronous neurotransmitter release. These results indicate that presynaptic structural remodeling can alter the spatial organization of neurotransmission and, through the membrane flow it generates, modulate its temporal precision.

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Publication Details

Journal
Science Advances
Published
2026-10-28
DOI
https://doi.org/10.1126/sciadv.aei2661
Primary Topic
Neuroscience and Neuropharmacology Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Presynaptic filopodia form kinapses and promote convective membrane flow to sustain synchronous neurotransmitter release

Alfredo Gonzalez‐Sulser, Jian Liu, Arthur F. Bikbaev, Sila K. Ultanir et al.
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Science Advances
Neuroscience and Neuropharmacology Research
article

Presynaptic filopodia form kinapses and promote convective membrane flow to sustain synchronous neurotransmitter release

Alfredo Gonzalez‐Sulser, Jian Liu, Arthur F. Bikbaev, Sila K. Ultanir, Michael Alan Cousin, Daniela Ivanova, Christian Rosenmund, Martin Heine, Jack F. Webster, Jana Kroll, Jon Moss, Rico Dong, Akanksha Jain
article en

Abstract

Synaptic plasticity is the principal mechanism by which neural circuits compute and adapt. Presynaptic plasticity is traditionally regarded as a transient adaptation of the synaptic vesicle fusion and recycling machinery, whereas the role of structural remodeling of synaptic boutons remains unclear. Here, we demonstrate a mechanical coupling between presynaptic structural remodeling and synaptic efficacy. We find that dynamic presynaptic filopodia emerge during active synaptic transmission and deform synaptic boutons while forming transient contacts with postsynaptic structures, which we term neuronal kinapses. Filopodia formation is activity dependent and occurs in intact circuits and human brain. Mechanistically, filopodial growth induces convective in-plane membrane flow toward the filopodium, accelerating release site clearance, a process associated with sustained release probability during repeated synaptic vesicle fusion. As a result, filopodia formation favors an increase in synchronous over asynchronous neurotransmitter release. These results indicate that presynaptic structural remodeling can alter the spatial organization of neurotransmission and, through the membrane flow it generates, modulate its temporal precision.

Science AdvancesVol. 12(44)
Roslin Institute (GB), Johns Hopkins University (US), Johannes Gutenberg University Mainz (DE), The Francis Crick Institute (GB), Humboldt-Universität zu Berlin (DE), Simons Initiative for the Developing Brain (GB), Freie Universität Berlin (DE), Charité - Universitätsmedizin Berlin (DE), University of Edinburgh (GB)
Simons Foundation, Johns Hopkins University, Wellcome Trust, Federation of European Biochemical Societies, Cancer Research UK, Royal Society, Epilepsy Research UK, Carnegie Trust for the Universities of Scotland, University of Edinburgh, Deutsche Forschungsgemeinschaft, National Institutes of Health, Medical Research Council
Openalex Percentile: Top 20%
Neuroscience and Neuropharmacology Research
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