Quantal size fits central synaptic depression

In this issue of PNAS, Chen et al. (1) report the first direct electrophysiological recordings from single visualized excitatory synapses and further define the elementary properties of chemical synaptic transmission. They show that single synapses of hippocampal neurons typically release one quantum of neurotransmitter and that presynaptic regulation of the size of this quantum contributes to short-term synaptic depression. Neural networks are defined by synaptic connections among neurons, typically chemical synapses, at which electrical signals are transmitted and received. The basic principles of chemical synaptic transmission were defined in pioneering studies of the neuromuscular junction and subsequently extended to synapses of the central nervous system (2–4). As illustrated in Fig. 1, axons often branch extensively before contacting postsynaptic targets where they form terminal compartments referred to as boutons. Presynaptic boutons contain many neurotransmitter-filled synaptic vesicles including a small, readily releasable pool docked at specialized plasma membrane structures called active zones (Fig. 1). After excitation of the presynaptic neuron, vesicle fusion and exocytosis of neurotransmitter is triggered by calcium influx through voltage-gated calcium channels. Subsequent activation of neurotransmitter-gated ion channels clustered within the postsynaptic density results in excitation or inhibition of the postsynaptic membrane. The vesicle hypothesis of neurotransmitter release provides a structural basis for the early observation that chemical synaptic transmission is quantal. One quantum likely corresponds to release of neurotransmitter from a single synaptic vesicle. Overview of synaptic structure and identification of isolated visualized single synapses. A branched axon, presynaptic boutons, and single-synapse structure are illustrated. In cultured hippocampal neurons, most boutons form only one synapse. Chen et al. visualized synapses by loading synaptic vesicles with the membrane-associated fluorescent dye FM 1-43 (green). To avoid inclusion …