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Journal of Neuroscience, Vol 14, 5325-5337, Copyright © 1994 by Society for Neuroscience
Changes in paired-pulse facilitation suggest presynaptic involvement in long-term potentiation
PE Schulz, EP Cook and D Johnston
Department of Neurology, Baylor College of Medicine, Houston, Texas 77030.
Long-term potentiation (LTP) is a use-dependent form of synaptic plasticity
that is of great interest as a potential cellular substrate underlying
memory. It is important to determine the pre- and/or postsynaptic locus of
LTP expression in order to study its underlying mechanisms. Despite
intensive investigation, however, its locus of expression remains
uncertain. It has been hypothesized that if LTP expression includes a
presynaptic locus then it may alter the expression of another
presynaptically mediated form of potentiation like paired-pulse
facilitation (PPF), which is an increase in a second population excitatory
postsynaptic potential when it is elicited shortly after a first. Previous
authors have found no change in PPF in association with LTP. We re-examined
the hypothesis, however, to reconcile the negative PPF data with other data
that have suggested presynaptic involvement in LTP. Extracellular
recordings were made in area CA1 of the rat hippocampal slice preparation.
Surprisingly, PPF both increased and decreased significantly in association
with LTP. The changes in PPF occurred in a predictable way, however. They
correlated inversely with initial PPF magnitude so that a larger initial
PPF was associated with a decrease in PPF with LTP while a smaller initial
PPF was associated with an increase. Because PPF increased or decreased in
individual slices in association with LTP, the average PPF of all slices
did not change, in agreement with previous studies. The changes in PPF were
also specific to LTP; that is, they were input specific, were not due to
changes in inhibition or nonspecific effects of high- frequency
stimulation, were not due to active postsynaptic currents or their
nonlinear summation, and PPF changed with the same time course as LTP. We
conclude that the mechanism of early LTP expression includes at least the
presynaptic locus. Two hypotheses regarding the presynaptic mechanism
underlying LTP expression, which are consistent with finding both increases
and decreases in PPF with LTP, are (1) that there is an increase in the
number of release sites with LTP or (2) that there is an increase in both
the number of release sites and the probability of neurotransmitter
release. Increases in the probability of neurotransmitter release alone
would not appear to account for our findings since such increases have been
associated only with decreases in PPF. Our findings do not exclude
additional postsynaptic involvement.(ABSTRACT TRUNCATED AT 400 WORDS)
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