The origin of Gaussian distributions of synaptic potentials.

Spontaneous synaptic potentials were identified at the motor endplate 40 years ago. These were shown to possess amplitudes that could be described by a Gaussian distribution as could the amplitudes of evoked synaptic potentials under conditions of very low probability for secretion. As these Gaussians were identical, the idea of a unit or quantum of transmission was conceived. The failure to obtain similar Gaussian distributions for both spontaneous and low-probability evoked potentials during development of endplates indicated that a unit of transmission was not operating. However both the spontaneous and very low-probability evoked potentials could each be described by mixtures of Gaussians indicating a subunit of transmission might be operative. There are no ganglionic or central synapses at which comparisons have been made between spontaneous and low-probability evoked potentials that show each can be described by a Gaussian distribution, let alone that these are the same indicating a unit of transmission as originally conceived. There is some evidence that mixtures of Gaussians can be used to describe both spontaneous and very low-probability evoked synaptic potential amplitudes, opening up the possibility for a subunit of transmission at these synapses. The vesicle hypothesis, that the quantum of transmission at the endplate is due to the exocytosis of the contents of a synaptic vesicle, was also enunciated nearly 40 years ago. The existence of subunits of transmission has required reconsideration of this hypothesis. Three alternatives are considered: in one, the calcium-transient hypothesis, the subunit of secretion is due to the release of calcium from one of several calcium stores in the nerve terminal, so that several subunits are released when a number of these calcium stores are engaged in a regenerative response to the terminal action potential; a second alternative, the mediatophore hypothesis, is that a subunit of secretion occurs when a single transmitter transport protein channels transmitter across the terminal membrane, several such mediatophore proteins acting in concert then give multiple subunit release; finally, there is the vesicle fusion-pore hypothesis, in which individual transient openings of a fusion-pore channel joining a synaptic vesicle to the terminal membrane are responsible for secretion of a transmitter subunit, with multiple transients giving several subunits. Perhaps we will have distinguished between these possibilities before the quantal hypothesis is 50 years old.