studied) and from the shape of the minis. The dis- 
tance out the dendritic tree of the synapse that pro- 
duces each mini is signaled by the mini shape, so 
synaptic contacts separated on dendrites are easily 
detected. The laboratory, then, has been able to 
carry out quantal analysis of synaptic transmission 
between hippocampal neurons in culture. 
Although minis at the neuromuscular junction 
vary little in size, the quantal size observed in hip- 
pocampal neuronal connections varies consider- 
ably, and one quantum is frequently two or three 
times as large as another. The shape of the mini 
size distribution is not Gaussian, but rather is 
skewed with a long tail to the larger minis. This dis- 
tribution can be accounted for quantitatively by the 
distribution of vesicle sizes observed in electron mi- 
crographs of cultured neurons. Because the minis 
vary so much in size, the equations that are used to 
determine quantal release parameters (probability 
of release and number of quanta ready for release) 
must be modified. 
Evoked release shows conspicuous fluctuations 
in the amplitude of individual currents, including 
occasional failures of release. These fluctuations 
have been studied for various extracellular magne- 
sium concentrations (a standard way to modify re- 
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lease probability); a standard theory assuming that 
the number of quanta released follows a binomial 
distribution provides an accurate description of the 
data, once the formalism is modified to take ac- 
count of the large fluctuations in mini amplitude. 
The agreement between observed and predicted 
synaptic current magnitudes is excellent. 
These experiments are the first satisfactory quan- 
tal analysis of central synaptic transmission. An 
important aspect of this work is the finding that 
central quanta vary considerably in size, at least in 
culture, so that this must be taken into account in 
the application of the theory. One important issue 
in long-term potentiation is whether the mecha- 
nism responsible for increased synaptic strength is 
pre- or postsynaptic. The only definitive way to de- 
termine the extent to which an increased efficacy in 
synaptic transmission is due to increased response 
to quanta or to altered release probability (to men- 
tion only two of the obvious possibilities) is through 
quantal analysis. Dr. Stevens and his colleagues 
plan to use their modified equations describing 
synaptic release to investigate this question. 
Dr. Stevens is also Professor of Molecular Neuro- 
biology at Yale University School of Medicine. 
Article 
Keana, J.F.W, McBurney R.N., Scherz, M.W, Fischer, J.B., Hamilton, EN., Smith, S.M., Server, A.C., Finkbeiner, 
S., Stevens, C.F., Jahr, C, and Weber, E. 1989. Synthesis and characterization of a series of diarylguanidines 
that are noncompetitive A^-methyl-D-aspartate receptor antagonists with neuroprotective properties. Proc 
Natl Acad Sci USA 86:5631-5635. 
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