Long-term effects of amygdala GABA receptor blockade on specific subpopulations of hippocampal interneurons
Long-term effects of amygdala GABA receptor blockade on specific subpopulations of hippocampal interneurons
复制标题
DOI：
10.1002/hipo.20002
复制
发表时间：
2004-01-01
期刊：
影响因子：
3.5
通讯作者：
Benes, FM
中科院分区：
文献类型：
--
作者：
Berretta, S;Lange, N;Benes, FM
越来越多的证据表明杏仁核调节海马体的功能。为了验证这一假设，即这种调制可能涉及海马神经元间网络的长期影响，在急性注入低剂量的GABA（A）受体拮抗剂印防己毒素进入杏仁核后96小时，在成年大鼠中评估了不同神经元间亚群特异性神经化学标志物表达的变化。齿状回（DG）和CA 4 -2区小清蛋白（PVB）免疫反应（IR）胞体的数密度（N-d）降低，而DG和CA 2区钙视网膜蛋白（CR）-IR的数密度降低。CA 3 -2细胞钙结合蛋白D28 k（CB）-IR胞体的N-d降低。PVB-IR和胆囊收缩素（CCK）-IR篮状神经元产生的轴突终末的密度也发生了变化，CCK-IR终末的密度在所有部门增加，而PVB-IR终末仅在CA区域减少。CCK-IR末端的增加被谷氨酸脱羧酶（GAD）65-kD亚型IR末端的增加所抵消（65）。混合效应的统计模型，特别是适应这些分析，表明杏仁输入海马的扰动显着改变海马PVB，CR-和CB-IR神经元在齿状回/CA 4区行使CCK-IR终端在同一区域内，以及在CA 3 -1的驱动器。这些结果表明，杏仁核调制特定的神经元亚群可能会引起持久的和深远的变化，在海马在正常运作，以及在疾病涉及杏仁核活动中断。特别是，在本研究结果中检测到的选择性海马区内的特定神经元间标记物的变化与精神分裂症中该区域的报道惊人相似。这些相似之处表明，在这种疾病中，杏仁核内GABA能传递的中断可能在海马异常的诱导中起重要作用。(C)2004 Wiley-Liss，Inc.
Growing evidence indicates that the amygdala modulates hippocampal functions. To test the hypothesis that this modulation may involve long-lasting effects on interneuronal networks in the hippocampus, changes in the expression of neurochemical markers specific for different interneuronal subpopulations were assessed in adult rats 96 h following acute infusion of low doses of the GABA(A) receptor antagonist picrotoxin into the amygdala. The numerical density (N-d) of somata showing immunoreactivity (IR) for parvalbumin (PVB) was decreased in dentate gyrus (DG) and the CA4-2 region, while that of calretinin (CR)-IR was decreased in DG and CA2. The N-d of calbindin D28k (CB)-IR somata was decreased in CA3-2. The densities of axon terminals arising from PVB-IR and cholecystokinin (CCK)-IR basket neurons were also altered, with those of CCK-IR terminals increased across all sectors, while PVB-IR terminals were decreased only in the CA region. Increases in CCK-IR terminals were paralleled by increases of terminals with IR for the 65-kD isoform of glutamate decarboxylase (GAD(65)). Mixed-effects statistical models, adapted specifically for these analyses, indicated that perturbations of amygdalar inputs to the hippocampus significantly alter the drive that hippocampal PVB-, CR-, and CB-IR neurons within the dentate gyrus/CA4 region exercise on CCK-IR terminals within the same region as well as in CA3-1. These results suggest that amygdalar modulation of specific neuronal subpopulations may induce lasting and far-reaching changes in the hippocampus during normal functioning, as well as in diseases involving a disruption of amygdalar activity. In particular, changes in specific interneuronal markers within selective hippocampal sectors detected in the present results are strikingly similar to those reported in this region in schizophrenia. These similarities suggest that, in this disease, a disruption of GABAergic transmission within the amygdala may play a significant role in the induction of abnormalities in the hippocampus. (C) 2004 Wiley-Liss, Inc.