In the mammalian brain, nerve cells exhibit large amplitude subthreshold membrane potential changes at their soma and dendrites. Using direct recordings from mossy fiber boutons (34 °C) of the granule cell-CA3 pyramidal cell synapse in the hippocampus, we studied the generation and function of subthreshold membrane potential changes in axons and presynaptic elements. We found that subthreshold analog signals generated in the dendrites propagate down the axon (0.5–1mm) in a decremental manner and enhance action potential-evoked transmitter release, whereas subtheshold signals in isolation fail to elicit postsynaptic signals (Alle and Geiger, 2006).. Thus, the postsynaptic signal contains information of both, the occurrence of a presynaptic action potential and the subthreshold membrane potential at the soma and dendrites of the neuron preceding the action potential. Hence, we propose that information transmission between neurons in local networks is based on a hybrid code of analog and digital signalling. In the presence of presynaptic 10 mM EGTA, a calcium chelator, a reduced but significant enhancement of action potential-evoked transmitter release by preceding analog signals remained. In addition, neither the presynaptic action potential waveform nor the action potential-evoked presynaptic calcium current was affected by the analog signals studied.. Therefore, our data are consistent with a partial direct voltage modulation of release machinery underlying enhancement of synaptic transmission by presynaptic subthreshold membrane potential changes at this synapse.