Langdon R B, Johnson J W, Barrionuevo G
Department of Neuroscience, University of Pittsburgh, Pennsylvania 15260, USA.
J Neurobiol. 1995 Mar;26(3):370-85. doi: 10.1002/neu.480260309.
A form of long-term potentiation (LTP) is induced at the mossy fiber (MF) synapse in the hippocampus by high-frequency presynaptic stimulation (HFS). It is generally accepted that induction of this form of LTP (MF LTP) does not depend on postsynaptic Ca2+ current gated by N-methyl-D-aspartate receptors, but it has remained controversial whether induction depends on postsynaptic depolarization and voltage-gated entry of Ca2+. There are also contradictory data on the time course of both LTP and post-tetanic potentiation (PTP), a shorter duration form of potentiation observed at MF synapses immediately following HFS. It has been proposed that some of these differences in results may have arisen because of difficulties in isolating monosynaptic responses to MF input. In the present study, whole cell recording was used to observe excitatory postsynaptic currents (EPSCs) elicited in CA3 pyramidal cells by input from MFs. Postsynaptic cells were dialyzed with 1,2-bis(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) and F- to inhibit postsynaptic mechanisms that required Ca2+, cells were under voltage clamp during HFS, and conditions were selected to minimize the likelihood of polysynaptic contamination. Under these conditions, HFS nevertheless induced robust LTP (mean magnitude, 62%). The possibility that EPSCs were contaminated by polysynaptic components was investigated by exposing the slices to a suppressing medium (one that partially blocked neurotransmission). EPSC waveforms did not change shape during suppression, indicating that contamination was absent. The LTP observed always was accompanied by prominent PTP that lasted through the first 5 to 15 min following HFS (mean decay time constant, 3.2 min). Induction of this LTP was not cooperative; there was no relationship between the size of responses and the magnitude of the LTP induced. LTP magnitude also was unrelated to the extent to which postsynaptic cells depolarized during HFS. These results show that high rates of presynaptic MF activity elicit robust LTP whether or not there is accompanying postsynaptic depolarization or increase in the concentration of postsynaptic Ca2+. High-frequency MF activity also results in a PTP that is unusually large and long.
通过高频突触前刺激（HFS）可在海马体的苔藓纤维（MF）突触处诱导出一种长时程增强（LTP）形式。人们普遍认为，这种形式的LTP（MF LTP）的诱导不依赖于由N-甲基-D-天冬氨酸受体门控的突触后Ca2+电流，但诱导是否依赖于突触后去极化和电压门控的Ca2+内流仍存在争议。关于LTP和强直后增强（PTP，HFS后立即在MF突触处观察到的一种持续时间较短的增强形式）的时间进程也存在相互矛盾的数据。有人提出，这些结果中的一些差异可能是由于分离对MF输入的单突触反应存在困难所致。在本研究中，采用全细胞记录来观察MF输入在CA3锥体细胞中引发的兴奋性突触后电流（EPSC）。用1,2-双（邻氨基苯氧基）乙烷-N,N,N',N'-四乙酸（BAPTA）和F-透析突触后细胞，以抑制需要Ca2+的突触后机制，在HFS期间将细胞置于电压钳制下，并选择条件以尽量减少多突触污染的可能性。在这些条件下，HFS仍能诱导出强烈的LTP（平均幅度为62%）。通过将切片暴露于抑制介质（一种部分阻断神经传递的介质）来研究EPSC是否被多突触成分污染。在抑制期间，EPSC波形没有改变形状，表明不存在污染。观察到的LTP总是伴随着显著的PTP，其持续到HFS后的最初5至15分钟（平均衰减时间常数为3.2分钟）。这种LTP的诱导不具有协同性；反应大小与诱导的LTP幅度之间没有关系。LTP幅度也与突触后细胞在HFS期间去极化的程度无关。这些结果表明，无论是否伴有突触后去极化或突触后Ca2+浓度增加，高频MF活动都会引发强烈的LTP。高频MF活动还会导致异常大且持续时间长的PTP。
