Increased vesicle fusion competence underlies long- term potentiation at hippocampal mossy fiber synapses

Presynaptic long-term potentiation (LTP) is thought to play an important role in learning and memory. However, the underlying mechanism remains elusive because of the difficulty of direct recording during LTP. Hippocam-pal mossy fiber synapses exhibit pronounced LTP of transmitter release after tetanic stimulation and have been used as a model of presynaptic LTP. Here, we induced LTP by optogenetic tools and applied direct presynaptic patch-clamp recordings. The action potential waveform and evoked presynaptic Ca2+ currents remained un-changed after LTP induction. Membrane capacitance measurements suggested higher release probability of synaptic vesicles without changing the number of release-ready vesicles after LTP induction. Synaptic vesicle replenishment was also enhanced. Furthermore, stimulated emission depletion microscopy suggested an in-crease in the numbers of Munc13-1 and RIM1 molecules within active zones. We propose that dynamic changes in the active zone components may be relevant for the increased fusion competence and synaptic vesicle replenishment during LTP.

Automated summary

This study reveals the important role of presynaptic long-term potentiation (LTP) in learning and memory. By using optogenetic tools and direct presynaptic patch-clamp recordings, the researchers found that LTP induction increased the release probability of synaptic vesicles without changing the number of release-ready vesicles. Enhanced synaptic vesicle replenishment and increased numbers of Munc13-1 and RIM1 molecules within active zones were also observed. These findings suggest that dynamic changes in active zone components may contribute to the increased fusion competence and synaptic vesicle replenishment during LTP.