Patterns of synaptic activity in neural networks recorded by light emission from synaptolucins.
Miesenböck G., Rothman JE.
The emission of light, coupled to exocytosis, can in principle be utilized to monitor the activity of a large number of individual synapses simultaneously. To illustrate this concept, fusion proteins of Cypridina luciferase and synaptotagmin-I or VAMP-2/synaptobrevin (which we term "synaptolucins") were expressed in cultured hippocampal neurons with the help of viral vectors. Synaptolucins were targeted to synaptic vesicles and, upon exocytosis, formed light-emitting complexes with their cognate luciferin, which was added to the extracellular medium. Photon emissions required a depolarizing stimulus, occurred from regions with high synaptic density as ascertained by vital staining of recycling synaptic vesicles, and were sensitive to Ca2+ depletion and clostridial neurotoxins. The method can currently detect exocytosis of the readily releasable pool of synaptic vesicles at a hippocampal synapse, corresponding to about two dozen quanta, but has the potential for greater sensitivity.