Locus coeruleus (LC) harbours a compact group of noradrenergic cell bodies projecting to virtually all parts of the central nervous system. Using combined measurements of amperometry and patch-clamp, quantal vesicle release of the transmitter was detected as amperometric spikes (ASs), following depolarization of the LC neurons. After a pulse depolarization the average latency of ASs was 1870 ms, while the latency of glutamate-mediated EPSCs was 1.6 ms. The ASs could be blocked by excluding the extracellular calcium which demonstrated the signal was calcium dependence;A substantial fraction of the depolarization-induced ASs originated from the somata,as tetrodotoxin could not block the depolarization-induced ASs.Furthermore, ASs and capacitance increase could be measured in acute isolated LC neuron. In contrast to glutamate-mediated EPSCs, noradrenaline (NA) secretion was strongly modulated by the action potential frequency (0.5-50 Hz), which the ASs increased during the higher firing frequency while decreased during spontaneous firing frequency. Somatodendritic NA release from LC upon enhanced cell activity produced autoinhibition of firing and of NA release. We conclude that, in contrast to classic synaptic transmission, quantal NA release from LC somata is characterized by a number of distinct properties, including long latency and high sensitivity to action potential frequency.