Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Brain Res. 2010 Apr 6;1323:65-73. doi: 10.1016/j.brainres.2010.01.090. Epub 2010 Feb 6.
The green fluorescent protein (GFP)-linked expression of protein in transgenic mice provides an ideal tool for the correlation of structure and function in the CNS. An important target of study is the role of GABAergic neurons in oscillatory activity in the hippocampus, and this would be facilitated with transgenic mice in which GFP is linked to the expression of GABA markers. One such mouse is the GAD67-GFP (Deltaneo), and here we compare the properties of kainate- and carbachol-induced oscillatory activity generated in CA3 of hippocampal slices from heterozygous GAD67-GFP (Deltaneo) mice and wild type litter mates. For both paradigms and in both mouse preparations oscillations were generated in the 20-30Hz range, and for the kainate-, but not the carbachol-induced oscillations, there was a small but significant difference in peak frequency of the oscillations between GAD67-GFP (Deltaneo) mice (28.4+/-2.2Hz) and wild type mice (25+/-1.6Hz). For both oscillatory paradigms there was no significant difference between mouse strains in area power of the oscillatory activity in the stratum oriens lamina of CA3, but for the kainate-induced oscillations, area power became significantly diminished in the stratum radiatum lamina of the GAD67-GFP (Deltaneo) mouse compared with the wild type mouse after prolonged exposure to kainate. This gradual reduction in area power in CA3 of the transgenic mouse was rescued by inclusion of Guvacine, a GABA uptake inhibitor, suggesting that the reported lower levels of GABA in the GAD67-GFP (Deltaneo) mouse brain during development and in the adult may contribute to a reduction in the efficiency of GABA neurotransmission after prolonged stimulation of the GABAergic circuitry.
绿色荧光蛋白(GFP)与转基因小鼠中蛋白质的表达相连接,为中枢神经系统(CNS)中结构与功能的相关性研究提供了理想的工具。一个重要的研究目标是 GABA 能神经元在海马体振荡活动中的作用,这将得益于 GFP 与 GABA 标志物表达相连接的转基因小鼠。其中一种小鼠是 GAD67-GFP(Deltaneo),在这里,我们比较了来自杂合 GAD67-GFP(Deltaneo)小鼠和野生型同窝小鼠海马 CA3 切片中海马体切片中由红藻氨酸和卡巴胆碱诱导的振荡活动的特性。对于这两种模型,在两种小鼠制备物中,振荡均在 20-30Hz 的范围内产生,并且对于红藻氨酸诱导的振荡,但不是卡巴胆碱诱导的振荡,在 GAD67-GFP(Deltaneo)小鼠(28.4+/-2.2Hz)和野生型小鼠(25+/-1.6Hz)之间存在一个小但显著的峰值频率差异。对于这两种振荡模型,在振荡活动的层状区域和 CA3 的辐射状层中,两种小鼠品系之间的区域功率没有显著差异,但对于红藻氨酸诱导的振荡,在长时间暴露于红藻氨酸后,GAD67-GFP(Deltaneo)小鼠的辐射状层中的区域功率显著降低。在转基因小鼠的 CA3 中,区域功率的这种逐渐降低可通过包括 GABA 摄取抑制剂 Guvacine 来挽救,这表明在发育中和成年期 GAD67-GFP(Deltaneo)小鼠大脑中报告的 GABA 水平较低可能导致 GABA 能神经传递的效率降低在 GABA 能电路长时间刺激后。