Brad Alger

This guy can effortlessly move from the molecular to the systems levels in both writing and speaking. I saw him present three posters at a time in New Orleans last month.

Anyway, here's some cool quotes from Jimok and Alger "Random Response Fluctuations Lead to Spurious Paired-Pulse Facilitation" J. Neurosci., 21(24):9608-9618. 2001. (OK, so it's a little old, but I'm just starting this blog).

"We show that spurious paired-pulse facilitation (PPF) can result from averaging randomly fluctuating PPRs because the method of calculating PPR as the mean of individual PPRs is biased in favor of high values of PPR. Spurious PPF can mask the intrinsic paired-pulse property of the synapses. Calculating PPR as the mean of the second response divided by the mean of the first avoids the error. We discuss a simple model that shows that spurious PPF depends on both the number of synapses recruited for release and the probability of release at each release site. The random factor can reconcile some conflicting published conclusions. "


"The PPR traditionally has been used for two main reasons: to determine whether a presynaptic or a postsynaptic effect occurred or to investigate the mechanism of a particular presynaptic effect. Our experiments show that spurious PPF can be produced by manipulations that affect presynaptic function. However, a nonuniform postsynaptic effect, one that altered the synaptic strength of a subset of synapses by affecting the probability of activation of receptor patches, for example, also could alter PPR by random effect. Thus changes in PPR probably cannot be used reliably to distinguish presynaptic from postsynaptic factors in cases in which CV is large and the mean(A2/A1) method is used. Finally, although we have focused on the spurious PPF that can occur when synaptic depression occurs, errors of interpretation in the opposite direction could occur as well. Consider an initial small response pair in which spurious PPF contributes to measured PPR. If an experimental treatment leads to larger initial responses and a decrease in relative response variability (CV), then a decrease in PPR will occur because of a decrease in spurious PPF. Because a decrease in PPR also is predicted by a use-dependent model of synapse strengthening, an erroneous conclusion concerning the mechanism of the effect could be drawn."