Schulz P E, Cook E P, Johnston D
Department of Neurology, Baylor College of Medicine, Houston, Texas 77030.
J Neurosci. 1994 Sep;14(9):5325-37. doi: 10.1523/JNEUROSCI.14-09-05325.1994.
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)
长时程增强（LTP）是一种依赖于使用的突触可塑性形式，作为记忆潜在的细胞基础备受关注。确定LTP表达的突触前和/或突触后位点对于研究其潜在机制很重要。然而，尽管进行了深入研究，其表达位点仍不确定。据推测，如果LTP表达包括突触前位点，那么它可能会改变另一种突触前介导的增强形式的表达，如双脉冲易化（PPF），即第二个群体兴奋性突触后电位在第一个之后不久引发时会增加。先前的作者发现PPF与LTP无关。然而，我们重新审视了这一假设，以使PPF的阴性数据与其他表明突触前参与LTP的数据相协调。在大鼠海马切片制备的CA1区进行细胞外记录。令人惊讶的是，PPF与LTP相关时显著增加和减少。然而，PPF的变化以可预测的方式发生。它们与初始PPF大小呈负相关，因此较大的初始PPF与LTP时PPF的减少相关，而较小的初始PPF与增加相关。由于与LTP相关时单个切片中的PPF增加或减少，所有切片的平均PPF没有变化，这与先前的研究一致。PPF的变化也特定于LTP；也就是说，它们是输入特异性的，不是由于抑制的变化或高频刺激的非特异性效应，不是由于活跃的突触后电流或其非线性总和，并且PPF与LTP具有相同的时间进程变化。我们得出结论，早期LTP表达的机制至少包括突触前位点。关于LTP表达基础的突触前机制的两个假设与LTP时PPF增加和减少的发现一致，即（1）LTP时释放位点的数量增加，或（2）释放位点的数量和神经递质释放的概率都增加。仅神经递质释放概率的增加似乎无法解释我们的发现，因为这种增加仅与PPF的减少相关。我们的发现不排除额外的突触后参与。（摘要截断于400字）
