Changes in paired-pulse facilitation suggest presynaptic involvement in long-term potentiation

Abstract

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)

Long-term potentiation involves increases in the probability of neurotransmitter release

“…It was previously shown that average PPF does not change with LTP, but PPF in individual slices does change (22), and the changes correlate with the magnitude of LTP induced (23). These results were confirmed recently (20,21).…”

“…Baseline p was greater in group 2 because of testing in the high-calcium saline. The 3-fold increase in calcium produces a 7.4-fold increase in pEPSP size elicited by the same stimulus intensity (22). And baseline p was less in group 3 because of adding -CgTX.…”

“…The hippocampi were dissected out and 400 m slices were made perpendicular to the septotemporal axis with a vibratome (Technical Products International, St. Louis). Slices were transferred to a Haas-type (25) interface recording chamber (Medical Systems, Greenvale, NY) at 32.5 Ϯ 0.1ЊC and maintained using standard procedures (22).…”

“…19). But PPF in individual slices does change: it increases or decreases depending on its initial value (20,21,22).…”

The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum

“…In control conditions, this protocol elicits a condition of Paired Pulse Facilitation (PPF), in which the amplitude of the FP elicited by the second stimulus (R2) is greater than the amplitude elicited by the first stimulus (R1). The degree of PPF is quantified by the R2/R1 ratio and a modification of this ratio is an indication of a presynaptic action on neurotransmitter release (Manabe et al, 1993;Schulz et al, 1994;Calabresi et al, 1997).…”