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The Journal of Neuroscience, December 15, 2001, 21(24):9608-9618
Random Response Fluctuations Lead to Spurious Paired-Pulse
Facilitation
Jimok
Kim1 and
Bradley
E.
Alger1, 2
1 Program in Neuroscience and 2 Department
of Physiology, University of Maryland School of Medicine, Baltimore,
Maryland 21201
We studied paired-pulse depression (PPD) of GABAAergic
IPSCs under conditions of reduced transmitter release (caused
by Cd2+, baclofen, or reduced stimulus intensity)
with whole-cell voltage clamp in CA1 pyramidal cells in
vitro. The use-dependent model of paired-pulse responsiveness
holds that a decrease in the probability of neurotransmitter release
during the first stimulus will cause predictable changes in the
paired-pulse ratio (PPR, the amplitude of the second IPSC divided by
that of the first). However, the applicability of the use-dependent
model to inhibitory synapses is controversial. Our results are
inconsistent with this model, but are consistent with the hypothesis
that random fluctuations in response size significantly influence PPR.
PPR was sensitive to the extracellular stimulus intensity in all
conditions. Changes in PPR were not correlated with changes in the
first IPSC, but were correlated with changes in variability of the PPRs
of individual traces. 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.
Key words:
short-term plasticity; neurotransmitter release; use
dependency; release probability; hippocampus; GABAergic IPSC
Copyright © 2001 Society for Neuroscience 0270-6474/01/21249608-11$05.00/0
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