Membrane mechanics of exo-endocytosis coupling encodes memory for presynaptic neuron short-term plasticity

Synapse is the unit of neural coding: It deciphers the information encoded through the temporal sequence of action potentials (AP) by the series of synaptic vesicle (SV) exocytosis on the presynaptic terminal, which transmits the neurotransmitters to signal the post-synaptic terminal. Rather than operating at steady state, synapse “memorizes” its experience of stimuli by long-term and short-term changes (aka, long-term plasticity (LTP) and short-term plasticity (STP), respectively). While LTP and STP on both presynaptic and postsynaptic terminals are essential in neural coding, the physical mechanisms that underlie any form of the synaptic plasticity are not well understood. Hereby, integrating theory and experiment we aim to elucidating the physical mechanisms underlying the STP on presynaptic terminals. In contrast to the previous models that rely on phenomenological descriptions, our model focuses on the membrane mechanics of synaptic transmission arising from the SV exo-endocytosis coupling, i.e., endocytosis retrieves the fused SVs to clear out the release sites for the next round of SV exocytosis on presynaptic terminal. Our results show that the membrane mechanics of SV exo-endocytosis coupling varies with the frequency, duration, and timing of AP stimuli, and provides the coherent physical mechanism for the different types of presynaptic STP. The resulting membrane mechanics on presynaptic terminal carries the memory of recent stimuli, defines the cellular state for synaptic transmission, and underlies the transition between the different types of presynaptic STP. Our finding suggests a key role of membrane mechanics in cellular memory that mediates transitions between cell states.