Wilson R I, Gödecke A, Brown R E, Schrader J, Haas H L
Institut für Neurophysiologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
Neuroscience. 1999;90(4):1157-65. doi: 10.1016/s0306-4522(98)00479-5.
Long-term potentiation, a persistent increase in synaptic efficacy, may require a retrograde signal originating in the postsynaptic cell that induces an increase in presynaptic neurotransmitter release. We have constructed a mouse homozygous for a targeted null mutation in the endothelial isoform of nitric oxide synthase and report that long-term potentiation in the CA1 region of these mice is entirely absent under weak stimulation conditions. Application of a membrane-permeant guanosine-3',5'-cyclic monophosphate analogue during tetanus fails to compensate for this deficit, suggesting that nitric oxide produced by endothelial nitric oxide synthase may affect long-term potentiation through a cascade that does not include guanylyl cyclase. We also report that strong tetanic stimulation can induce robust long-term potentiation in these mice which is not blocked by pharmacological inhibitors of nitric oxide synthase. Furthermore, mice lacking endothelial nitric oxide synthase show no shift in the frequency-response curve for the induction of long-term potentiation. Basal synaptic transmission, paired-pulse facilitation and the electrical properties of CA1 cells in these mice were similar to controls. These results support a selective role for endothelial nitric oxide synthase in long-term potentiation, but also demonstrate that nitric oxide synthase is not involved in this process under all conditions.
长时程增强，即突触效能的持续增加，可能需要一个源自突触后细胞的逆行信号，该信号诱导突触前神经递质释放增加。我们构建了一种小鼠，其内皮型一氧化氮合酶存在靶向无效突变且为纯合子，并报告称在弱刺激条件下，这些小鼠CA1区的长时程增强完全缺失。在强直刺激期间应用一种可透过膜的鸟苷 - 3',5'-环磷酸类似物无法弥补这一缺陷，这表明内皮型一氧化氮合酶产生的一氧化氮可能通过不包括鸟苷酸环化酶的级联反应影响长时程增强。我们还报告称，强强直刺激可在这些小鼠中诱导强烈的长时程增强，而一氧化氮合酶的药理学抑制剂并不能阻断这种增强。此外，缺乏内皮型一氧化氮合酶的小鼠在长时程增强诱导的频率 - 反应曲线上没有偏移。这些小鼠的基础突触传递、双脉冲易化以及CA1细胞的电特性与对照相似。这些结果支持内皮型一氧化氮合酶在长时程增强中具有选择性作用，但也表明一氧化氮合酶并非在所有条件下都参与这一过程。
