Doyle C, Hölscher C, Rowan M J, Anwyl R
Department of Physiology, Trinity College, Dublin 2, Ireland.
J Neurosci. 1996 Jan;16(1):418-24. doi: 10.1523/JNEUROSCI.16-01-00418.1996.
The membrane-permeant gas NO is a putative intercellular messenger that has been proposed on the basis of previous in vitro studies to be involved in synaptic plasticity, especially the induction of long-term potentiation (LTP) of excitatory synaptic transmission in the hippocampus and cortex. In the present study, the role of NO in synaptic plasticity has been investigated in vivo. In particular, the action of the novel and selective neuronal NO synthase (nNOS) inhibitor 7-nitro-indazole (7-NI) has been investigated on the induction of LTP and depotentiation (DP) of field EPSPs in CA1 of the hippocampus in vivo. Unlike previously studied nonselective NOS inhibitors, 7-NI does not increase arterial blood pressure. In vehicle-injected rats, high-frequency stimulation consisting of a series of trains at 200 Hz induced LTP. However, LTP induction was strongly inhibited in 7-NI (30 mg/kg, i.p.)-treated animals. The inhibitory effect of 7-NI on the induction of LTP was prevented by pretreatment with L-arginine, the substrate amino acid used by NOS. In control animals, low-frequency stimulation consisting of 900 stimuli at 10 Hz induced DP of previously established LTP, whereas in 7-HI-treated animals only a short-term depression was induced. This effect of 7-NI also was prevented by D-arginine. The LTP and DP induced in control animals in this study were NMDA receptor-dependent, the NMDA receptor antagonist 3-(R,S)-2-carboxypiperazin-4-yl-propyl-1- phosphonic acid inhibiting the induction of both forms of synaptic plasticity. The present experiments are the first to demonstrate that an NOS inhibitor blocks the induction of the synaptic component of LTP and DP in vivo and, therefore, these results strengthen evidence that the production of NO is necessary for the induction of LTP and DP.
可透过细胞膜的气体一氧化氮（NO）被认为是一种细胞间信使，基于以往的体外研究，它被认为参与突触可塑性，特别是海马体和皮层中兴奋性突触传递的长时程增强（LTP）的诱导。在本研究中，已在体内研究了NO在突触可塑性中的作用。特别地，研究了新型选择性神经元型一氧化氮合酶（nNOS）抑制剂7-硝基吲唑（7-NI）对体内海马体CA1区场兴奋性突触后电位（fEPSP）的LTP诱导和去增强作用（DP）的影响。与先前研究的非选择性NOS抑制剂不同，7-NI不会升高动脉血压。在注射溶剂的大鼠中，由一系列200Hz的串刺激组成的高频刺激诱导了LTP。然而，在经7-NI（30mg/kg，腹腔注射）处理的动物中，LTP诱导受到强烈抑制。用L-精氨酸（NOS使用的底物氨基酸）预处理可防止7-NI对LTP诱导的抑制作用。在对照动物中，由10Hz的900次刺激组成的低频刺激诱导了先前建立的LTP的DP，而在经7-HI处理的动物中仅诱导了短期抑制。7-NI的这种作用也可被D-精氨酸阻止。本研究中对照动物诱导的LTP和DP是NMDA受体依赖性的，NMDA受体拮抗剂3-(R,S)-2-羧基哌嗪-4-基-丙基-1-膦酸抑制这两种形式的突触可塑性的诱导。本实验首次证明，一种NOS抑制剂在体内可阻断LTP和DP的突触成分的诱导，因此，这些结果强化了NO的产生对于LTP和DP的诱导是必需的这一证据。
