Partitioning the synaptic landscape: distinct microdomains for spontaneous and spike-triggered neurotransmission

For over 50 years, it has been recognized that two distinct modes of neurotransmission are operative at synapses: the release of neurotransmitter triggered by the invasion of action potentials into presynaptic terminals and spontaneous neurotransmitter release that occurs independently of action potentials. In the past, spontaneous neurotransmitter release has been dismissed as mere synaptic noise, but recent studies have suggested that spontaneous release has important functional roles at synapses. New evidence indicates that spontaneous release and action potential-evoked release preferentially activate distinct subsets of postsynaptic receptors, suggesting that synapses use physically segregated pathways to decode spontaneous and evoked neurotransmission.