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.