Munc18-1 expression levels control synapse recovery by regulating readily releasable pool size

Prompt recovery after intense activity is an essential feature of most mammalian synapses. Here we show that synapses with reduced expression of the presynaptic gene munc18-1 suffer from increased depression during intense stimulation at glutamatergic, GABAergic, and neuromuscular synapses. Conversely, munc18-1 overexpression makes these synapses recover faster. Concomitant changes in the readily releasable vesicle pool and its refill kinetics were found. The number of vesicles docked at the active zone and the total number of vesicles per terminal correlated with both munc18-1 expression levels and the size of the releasable vesicle pool. These data show that varying expression of a single gene controls synaptic recovery by modulating the number of docked, release-ready vesicles and thereby replenishment of the secretion capacity.