Calyceal synapses transmit information at high rates, with sub-millisecond temporal precision. During the first funding period, we studied the roles of piccolo, bassoon and RIM-binding protein 2. Our studies also revealed a high heterogeneity of synaptic transmission and short-term plasticity. We propose that synaptic modulation through transmitters such as dopamine (DA), serotonin (5-HT), or noradrenalin (NE) contributes to the control of synaptic function, and is therefore responsible for this heterogeneity. We will test this by a combination of electrophysiology, optogenetics and imaging approaches.