Parsing spontaneous and evoked neurotransmission on both sides of the synapse.

Editor's Note: These short, critical reviews of recent papers in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to summarize the important findings of the paper and provide additional insight and commentary. For more information on the format and purpose of the Journal Club, please see Review of Chung et al. At least three distinct forms of synaptic transmission have been described at exci-tatory and inhibitory synapses in the CNS. Under resting conditions, presynaptic terminals spontaneously release individual synaptic vesicles, producing miniature postsynaptic currents. When a presynap-tic terminal is invaded by an action potential , two phases of evoked vesicle release ensue: a synchronous phase that is rapid and coordinated, and an asynchronous phase that is delayed and prolonged. Classic theories of quantal synaptic transmission assume that the same presynaptic vesicles are recruited by spontaneous and evoked neurotransmission, but emerging evidence suggests spontaneous and evoked release actually draw from two distinct pools of vesicles (Sara et al. A recent report by Chung et al. (2010) in The Journal of Neuroscience has further clarified this issue by comparing the mechanism of synaptic vesicle recycling following evoked and spontaneous release. Recycling involves the retrieval of fused vesicles from the plasma membrane through endocytosis, which typically requires dynamin GTPase to split vesicle membrane from plasma membrane. The authors first confirmed that the GTPase activity of dynamin was reduced by dynasore, a selective inhibitor of dynamin 1 and 2. They also confirmed that dynasore impaired synaptic vesicle recycling in cultured hippocampal neurons, by infecting these neurons with synaptophysin-pHlu-orin. This construct is delivered to synaptic vesicles and fluoresces when vesicles fuse with the plasma membrane, but its fluores-cence is normally quenched after vesicle en-docytosis. Following brief stimulation, the synaptophysin-pHluorin signal persisted in the presence of dynasore, confirming that dynamin function is necessary for the normal retrieval of vesicles that fuse during evoked neurotransmission. Chung et al. (2010) went on to examine whether dynasore impairs vesicle recycling in cultured hippocampal neurons, using whole-cell voltage-clamp recordings from individual pyramidal neurons. In contrast to this group's previous work on excitatory synapses (Sara et al., 2005), these experiments focused on inhibitory synapses, which prominently exhibit spontaneous vesicle release as well as synchronous and asynchronous evoked release. Evoked inhibitory currents were progressively reduced in the presence of dynasore, indicating that dynamin-dependent vesicle recycling is necessary to maintain evoked in-hibitory neurotransmission. Surprisingly, exposure to dynasore for up …