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Old innovations and shifted paradigms in cellular neuroscience

Riccardo Fesce · Frontiers in Cellular Neuroscience · 2024

Once upon a time the statistics of quantal release were fashionable: “n” available vesicles (fusion sites), each with probability “p” of releasing a quantum. The story was not so simple, a nice paradigm to be abandoned. Biophysicists, experimenting with “black films,” explained the astonishing rapidity of spike-induced release: calcium can trigger the fusion of lipidic vesicles with a lipid bilayer, by masking the negative charges of the membranes. The idea passed away, buried by the discovery of NSF, SNAPs, SNARE proteins and synaptotagmin, Munc, RIM, complexin. Electrophysiology used to be a field for few adepts. Then came patch clamp, and multielectrode arrays and everybody became electrophysiologists. Now, optogenetics have blossomed, and the whole field has changed again. Nice surprise for me, when Alvarez de Toledo demonstrated that release of transmitters could occur through the transient opening of a pore between the vesicle and the plasma-membrane, no collapse of the vesicle in the membrane needed: my mentor Bruno Ceccarelli had cherished this idea (“kiss and run”) and tried to prove it for 20 years. The most impressive developments have probably regarded IT, computers and

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