Gilbert M E, Mack C M
National Research Council, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Brain Res. 1998 Apr 6;789(1):139-49. doi: 10.1016/s0006-8993(97)01517-5.
Long-term potentiation (LTP) is a model of synaptic plasticity believed to encompass the underlying neurobiological mechanisms that support memory function. Chronic developmental lead (Pb) exposure is known to be associated with cognitive dysfunction in children and animals. Disruption of the induction of long-term potentiation (LTP) has been reported in the hippocampus following chronic exposure to environmentally relevant levels of Pb in rats. Under urethane anesthesia, we have previously observed Pb-induced increases in the threshold for LTP induction. With higher train intensities, LTP was induced and no declines in the amplitude of responses within a 60-min posttrain period were evident. The present study was designed to assess the effects of Pb on the more enduring forms of LTP in the dentate gyrus of the conscious rat. Beginning in the late gestational period, 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, electrodes were permanently implanted in male offspring and field potentials evoked by perforant path stimulation were recorded from the dentate gyrus over several weeks. LTP was induced by delivering theta-burst patterned stimulation at a maximal stimulus intensity through the perforant path electrode, and input/output (I/O) functions were monitored for 1 month. Population spike (PS) amplitude was increased maximally 1 h after train delivery. The time constant of decay (tau) calculated from pooled data for each group yielded declines in PS amplitude by 63% in 17.4 days in controls and 13.4 days in Pb-exposed animals. Quantitative estimates of decay in individual animals were achieved in two ways: (1) by calculating difference scores in I/O functions from the maximal LTP at 1 h, and (2) by interpolating day to decay by 63% from declines from maximal LTP. The interpolated values were used to compare the incidence of animals showing decay of 63% within 1 week posttrain. Both analyses revealed a more accelerated rate of decay of LTP in animals developmentally exposed to Pb relative to controls. Endurance of potentiated responses for days to weeks is believed to be supported by structural modifications and synaptic growth. The reported effects of Pb on growth-related processes may thus contribute to a reduced persistence of LTP and the resulting cognitive deficits engendered by developmental Pb exposure.
长时程增强（LTP）是一种突触可塑性模型，被认为包含支持记忆功能的潜在神经生物学机制。已知长期发育性铅（Pb）暴露与儿童和动物的认知功能障碍有关。据报道，在大鼠长期暴露于环境相关水平的Pb后，海马体中长时程增强（LTP）的诱导受到破坏。在乌拉坦麻醉下，我们之前观察到Pb诱导LTP诱导阈值升高。在更高的刺激强度下，诱导出了LTP，并且在训练后60分钟内反应幅度没有明显下降。本研究旨在评估Pb对清醒大鼠齿状回中更持久形式的LTP的影响。从妊娠后期开始，大鼠通过怀孕母鼠的饮用水长期暴露于0.2%的Pb（2+）-醋酸盐中，并在断奶后直接通过它们自己的供水系统暴露。成年后，将电极永久植入雄性后代体内，并在数周内记录来自齿状回的穿通路径刺激诱发的场电位。通过穿通路径电极以最大刺激强度给予theta波爆发式刺激来诱导LTP，并监测输入/输出（I/O）功能1个月。群体峰电位（PS）幅度在训练后1小时达到最大增加。根据每组的汇总数据计算的衰减时间常数（tau）显示，对照组中PS幅度在17.4天内下降了63%，而铅暴露动物在13.4天内下降。通过两种方式对个体动物的衰减进行了定量估计：（1）通过计算从1小时的最大LTP开始的I/O功能差异分数，（2）通过从最大LTP的下降中插值推算出衰减63%所需的天数。插值后的值用于比较在训练后1周内衰减63%的动物发生率。两种分析都表明，与对照组相比，发育性暴露于Pb的动物中LTP的衰减速度更快。增强反应持续数天至数周的能力被认为是由结构改变和突触生长所支持的。因此，所报道的Pb对与生长相关过程的影响可能导致LTP的持久性降低以及发育性铅暴露所产生的认知缺陷。
