EFFECTS OF PRENATAL PROTEIN-MALNUTRITION ON KINDLING-INDUCED ALTERATIONS IN DENTATE GRANULE CELL EXCITABILITY .2. PAIRED-PULSE MEASURES
EFFECTS OF PRENATAL PROTEIN-MALNUTRITION ON KINDLING-INDUCED ALTERATIONS IN DENTATE GRANULE CELL EXCITABILITY .2. PAIRED-PULSE MEASURES
复制标题
DOI：
10.1016/0014-4886(91)90072-k
复制
发表时间：
1991-05-01
影响因子：
5.3
通讯作者：
GALLER, JR
中科院分区：
文献类型：
--
作者：
BRONZINO, JD;AUSTINLAFRANCE, RJ;GALLER, JR
产前蛋白质营养不良的影响点燃诱导的变化，抑制调制的齿状回颗粒细胞活性进行了检查，通过分析记录的细胞外场电位从齿状回颗粒细胞层的成对脉冲刺激的自由移动大鼠的穿通通路。由于我们已经表明，点燃的结果在增强的突触传递水平上的穿通路径/颗粒细胞突触（见前一份文件），我们试图确定点燃过程是否可能会引起变化的抑制性调节颗粒细胞兴奋性，这可能涉及到较慢的收购点燃状态，我们以前报道的营养不良的动物。从120-150日龄开始，以20-1000 ms的脉冲间隔（IPI）检查齿状颗粒细胞对穿孔路径配对脉冲刺激的反应。配对脉冲指数（PPI）是根据应用脉冲对产生的两种反应的群体尖峰振幅的平均百分比变化来构建的。PPI测量点燃过程中获得的比较与个人预点燃措施，以确定颗粒细胞活性的兴奋/抑制调制的平均百分比变化。在第一次点燃后放电后，两个饮食组的所有IPIs检测均明显抑制了第二次群体反应。这种抑制包括早期（IPIs≤ 40 ms）和晚期（IPIs≥ 300 ms）抑制期期间抑制调节水平的显着增强，以及易化期（IPIs> 40 ms但< 300 ms）的完全消失，在第一次点燃后放电后，被第二次群体反应的抑制所取代。在此抑制性调节颗粒细胞兴奋性的增强程度显着更大的营养不良组的动物在所有IPIs以上30毫秒。显着增强的抑制水平保持由两个饮食组的动物在整个点燃期间，表明在齿状回，点燃不伴随着减少或损失的颗粒细胞活性的抑制性调节。然而，点燃停止后一周，发现6%-25%饮食组动物的增强抑制水平显著降低，而对照饮食组动物继续显示与第一阶段5惊厥后记录的水平相同的增强抑制活性水平。我们的研究结果表明，产前蛋白质营养不良诱导的抑制系统的活动调节齿状颗粒细胞的活动，从而显着增强点燃诱导的双脉冲抑郁症的改变。这些变化在6% 25%饲料组动物中似乎是暂时的，但在对照饲料组动物中具有更持久的性质。我们认为，这种增强的抑制可能直接相关的点燃的速度较慢，并相对不能始终达到点燃状态，我们已经观察到营养不良的动物。与前一篇论文的结果相似，产前饮食损伤的影响在成熟动物中似乎是不可逆的，即使经过长时间的饮食恢复。
The effects of prenatal protein malnutrition on kindling-induced changes in inhibitory modulation of dentate granule cell activity were examined by analysis of extracellular field potentials recorded from the granule cell layer of the dentate gyrus in response to paired-pulse stimulation of the perforant pathway in freely-moving rats. Since we have shown that kindling results in enhanced synaptic transmission at the level of the perforant path/granule cell synapse (see preceding paper), we sought to determine if the kindling process might induce changes in inhibitory modulation of granule cell excitability which could be involved in the slower acquisition of the kindled state we have previously reported in malnourished animals. Beginning at 120–150 days of age, the response of dentate granule cells to paired-pulse stimulation of the perforant path was examined at interpulse intervals (IPIs) ranging from 20–1000 ms. A paired-pulse index (PPI) was constructed based on the mean percent change in population spike amplitudes of the two responses resulting from application of the pulse pair. PPI measures obtained during the kindling process were compared with individual prekindling measures to determine the mean percent change in excitatory/inhibitory modulation of granule cell activity. Significant inhibition of the second population response was apparent at all IPIs tested for both diet groups following the first kindled afterdischarge. This inhibition included significantly enhanced levels of inhibitory modulation during both the early (IPIs≤ 40 ms) and late (IPIs≥ 300 ms) inhibitory phase, as well as a complete disappearance of the facilitation phase (IPIs> 40 ms but< 300 ms) which was replaced, following the first kindled afterdischarge, by inhibition of the second population response. The degree of enhancement in this inhibitory modulation of granule cell excitability was significantly greater in the animals of the malnourished group at all IPIs above 30 ms. Significantly enhanced levels of inhibition were maintained by animals of both diet groups throughout the kindling period, indicating that within the dentate gyrus, kindling is not accompanied by a decrease or loss of inhibitory modulation of granule cell activity. One week after cessation of kindling, however, the level of enhanced inhibition was found to be significantly reduced in animals of the 6% 25% diet group, while animals of the control diet group continued to show levels of enhanced inhibitory activity of the same magnitude as those recorded following the first stage 5 convulsion. Our results indicate that prenatal protein malnutrition induces alterations in the activity of inhibitory systems modulating dentate granule cell activity resulting in significant enhancement of kindling-induced paired-pulse depression. These alterations appear to be transitory in animals of the 6% 25% diet group, but of a more enduring nature in animals of the control diet group. We suggest that this enhancement of inhibition may be directly related to both the slower rate of kindling and the relative inability to consistently attain the kindled state which we have observed in malnourished animals. Paralleling results of the preceding paper, the effects of the prenatal dietary insult appear to be irreversible in mature animals even after a prolonged period of dietary rehabilitation.