Temporal coupling of axonal calcium responses and filopodia formation

The combination of synaptic structural stability and functional plasticity is a recognized feature of the nervous system. This dichotomy is possible because the processes involved in neuronal information processing, such as receiving and transducing stimuli and generating synaptic responses, are predominantly biochemical. Here, we reveal a presynaptic response to neuronal activity that is physical in nature. We show that dynamic filopodia emerge and transiently deform synaptic boutons to enhance connectivity during action potential discharge. Filopodia extension increases presynaptic membrane tension, which is crucial for preserving synchronous neurotransmitter release during repeated synaptic vesicle fusion. However, during excessive action potential discharge, this mechanism becomes maladaptive, contributing to epileptogenesis. Therefore, we provide the first direct evidence that mechanical forces determine the extent and timescale of synaptic signals.