Gilbert M E, Mack C M, Lasley S M
National Research Council, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Brain Res. 1996 Oct 14;736(1-2):118-24. doi: 10.1016/0006-8993(96)00665-8.
Chronic developmental lead (Pb) exposure has been long associated with cognitive dysfunction in children and animals. In an attempt to more directly relate the behavioral observations of impaired cognitive ability to Pb-induced effects on neuronal activity, we utilized the long-term potentiation (LTP) model of neural plasticity to assess synaptic function. Male rats were chronically exposed to 0.2% Pb(2+)-acetate through the drinking water of the pregnant dam, and directly through their own water supply at weaning. As adults, field potentials evoked by perforant path stimulation were recorded in the dentate gyrus under urethane anesthesia. LTP threshold was determined by applying a series of stimulus trains of increasing intensities. Baseline testing of dentate gyrus field potentials indicated that input/output functions, maximal response amplitudes, and threshold currents required to evoke a population spike (PS) did not differ for control and Pb-exposed animals. Despite similarities in baseline synaptic transmission, Pb-exposed animals required a higher train intensity to evoke LTP than controls. With maximal train stimulation, however, control and Pb animals exhibited comparable levels of potentiation. These findings suggest that the mechanisms of LTP induction are preferentially impaired by Pb exposure. Although baseline synaptic transmission was not altered in Pb-exposed animals, decreases in glutamate release following high K+ perfusion and reductions in paired pulse facilitation have been reported in the intact animal. Pb-induced reductions in calcium influx through voltage-sensitive or N-methyl-D-aspartate (NMDA) receptor-dependent channels may mediate increases in LTP threshold. It is possible that the threshold changes in the induction of LTP reported here contribute to cognitive impairments associated with Pb exposure.
长期的发育性铅（Pb）暴露一直以来都与儿童和动物的认知功能障碍有关。为了更直接地将认知能力受损的行为观察结果与铅对神经元活动的影响联系起来，我们利用神经可塑性的长时程增强（LTP）模型来评估突触功能。雄性大鼠在孕期通过母鼠饮用水长期暴露于0.2%的醋酸铅（Pb²⁺）中，并在断奶后直接通过它们自己的供水系统暴露于该物质。成年后，在乌拉坦麻醉下记录齿状回中穿通路径刺激诱发的场电位。通过施加一系列强度递增的刺激序列来确定LTP阈值。齿状回场电位的基线测试表明，对照组和铅暴露组动物在输入/输出功能、最大反应幅度以及诱发群体峰电位（PS）所需的阈值电流方面没有差异。尽管基线突触传递存在相似性，但与对照组相比，铅暴露组动物需要更高强度的刺激序列才能诱发LTP。然而，在最大刺激序列刺激下，对照组和铅暴露组动物表现出相当的增强水平。这些发现表明，LTP诱导机制优先受到铅暴露的损害。尽管铅暴露组动物的基线突触传递没有改变，但在完整动物中已报道高钾灌注后谷氨酸释放减少以及成对脉冲易化作用降低。铅诱导的通过电压敏感性或N-甲基-D-天冬氨酸（NMDA）受体依赖性通道的钙内流减少可能介导了LTP阈值的升高。此处报道的LTP诱导阈值变化可能导致与铅暴露相关的认知障碍。
