Neurons are arranged in networks in which they communicate between each other by the means of synapses. Synaptic transmission can undergo activity-dependent and short-lived changes in strength, known as short-term synaptic plasticity. Short-term plasticity is an important mechanism for neural networks in living organisms, which plays a role in adaptation to sensory inputs and information processing. One of the interesting forms of short-term enhancement in transmitter release is post-tetanic potentiation (PTP). PTP is generated upon repetitive activity of the synapse and lasts tens of seconds to minutes. A more detailed understanding of the molecular mechanisms of short-term plasticity will be helpful to understand information processing in neural networks. Here, I studied the cellular and molecular basis of post-tetanic potentiation at the calyx of Held model synapse. Pharmacological inhibition of conventional protein kinase C (cPKC) isoforms resulted in a near- complete block of PTP. This showed that cPKC dependent phosphorylation of a target presynaptic protein is a key process underlying PTP. Upon inhibition of phosphatases by calyculin, PTP was remarkably prolonged, by the suppression of dephosphorylation. By expressing a FRET (Fluorescence Resonance Energy Transfer) based PKC activity probe, I obtained independent evidence for transient activation of cPKC during PTP. This refers to a transient phosphorylation/dephosphorylation, which underlies the short-term changes in the release probability during PTP. To investigate the target protein, which becomes phosphorylated by PKC during PTP, I studied phosphorylation of the presynaptic protein Munc18-1. By establishing a virus-mediated in vivo gene-replacement approach using floxed Munc18-1 mice, we replaced endogenous Munc18-1 with phosphorylation-deficient form of Munc18-1. I showed that in the nerve terminals expressing the phosphorylation deficient form of Munc18-1, PTP was strongly suppressed as compared to the wild type form of Munc18-1. This PhD thesis work proposes a molecular model for PTP in which a transient phosphorylation/dephosphorylation of Munc18-1 by conventional PKCs and phosphatases, respectively modulates the calcium sensitivity of vesicle fusion and determines the kinetics of PTP.