Attenuated LTP in hippocampal dentate gyrus neurons of mice deficient in the PAF receptor
Attenuated LTP in hippocampal dentate gyrus neurons of mice deficient in the PAF receptor
复制标题
DOI：
10.1152/jn.2001.85.1.384
复制
发表时间：
2001-01-01
影响因子：
2.5
通讯作者：
Bazan, NG
中科院分区：
文献类型：
--
作者：
Chen, C;Magee, JC;Bazan, NG
血小板活化因子是一种来源于磷脂酶A(2)和其他途径的生物活性脂质(1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine)，与神经可塑性和记忆形成有关。长时程增强(LTP)可由PAF诱导，并被PAF受体(PAF-R)抑制剂阻断在CA1区和齿状回。为了进一步研究PAF在突触可塑性中的作用，我们比较了PAF-R缺乏的成年小鼠和年龄匹配的野生型小鼠海马片齿状颗粒细胞中的LTP。全细胞膜片钳记录采用电流钳模式。用高频刺激(HFS)诱导穿支通路LTP，定义为HFS后26~30min兴奋性突触后电位(EPSPS)幅度较基线增加20%。与野生型小鼠(219+/-17%，n=32)相比，PAF-R缺陷小鼠细胞内HFS诱导的EPSP幅度的增强作用减弱(163+/-14%，平均值+/-SE；n=32)。缺陷小鼠的LTP诱导率(72%，23/32个细胞)也低于野生型小鼠(91%，29/32个细胞)。以双脉冲易化作为突触通路的判别指标，两组间外侧穿支路径LTP波幅有差异，而内侧穿支路径LTP波幅无明显差异。PAF突触体受体拮抗剂BN52021(5um)可降低野生型小鼠外侧通路的LTP。然而，BN52021和微粒体PAF-R拮抗剂BN50730(5um)都不能减少受体缺陷小鼠侧支通路中的LTP。这些数据为PAF-R缺陷小鼠是研究齿状回LTP的有用模型提供了证据，并支持PAF积极参与海马突触可塑性的观点。
Platelet-activating factor (PAF), a bioactive lipid (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) derived from phospholipase A(2) and other pathways, has been implicated in neural plasticity and memory formation. Long-term potentiation (LTP) can be induced by the application of PAF and blocked by a PAF receptor (PAF-R) inhibitor in the hippocampal CA1 and dentate gyrus. To further investigate the role of PAF in synaptic plasticity, we compared LTP in dentate granule cells from hippocampal slices of adult mice deficient in the PAF-R and their age-matched wild-type littermates. Whole cell patch-clamp recordings were made in the current-clamp mode. LTP in the perforant path was induced by a high-frequency stimulation (HFS) and defined as >20% increase above baseline of the amplitude of excitatory postsynaptic potentials (EPSPs) from 26 to 30 min after HFS. HFS-induced enhancement of the EPSP amplitude was attenuated in cells from the PAF-R-deficient mice (163 +/- 14%, mean +/- SE; n = 32) when compared with that in wild-type mice (219 +/- 17%, n = 32). The incidence of LTP induction was also lower in the cells from the deficient mice (72%, 23 of 32 cells) than in the wild-type mice (91%, 29 of 32 cells). Using paired-pulse facilitation as a synaptic pathway discrimination, it appeared that there were differences in LTP magnitudes in the lateral perforant path but not in the medial perforant path between the two groups. BN52021 (5 muM), a PAF synaptosomal receptor antagonist, reduced LTP in the lateral path in the wild-type mice. However, neither BN52021, nor BN50730 (5 muM), a microsomal PAF-R antagonist, reduced LTP in the lateral perforant path in the receptor-deficient mice. These data provide evidence that PAF-R-deficient mice are a useful model to study LTP in the dentate gyrus and support the notion that PAF actively participates in hippocampal synaptic plasticity.