AG Entwicklungsneurobiologie, Fakultät für Biologie and Biotechnologie, ND 6/72, Ruhr-Universität, 44780 Bochum, Germany.
Exp Brain Res. 2009 Dec;199(3-4):265-78. doi: 10.1007/s00221-008-1688-y.
The synRas transgenic mice express constitutively activated Valin12-Harvey Ras in postnatal neocortical pyramidal neurons. This leads to somatodendritic hypertrophy, higher densities of spines and synapses, and an enhancement of synaptic long-term potentiation associated with an increased glutamate receptor-mediated activity. It was less clear how the interneurons respond to these alterations, and this prompted the quantitative assessment of interneuron neurochemistry. Interneurons rarely expressed the transgene, however, several interneuron types displayed a transient somatic hypertrophy. Furthermore, NPY mRNA expression was persistently increased as were the laminar percentages of labeled neurons. The expression of parvalbumin and voltage-gated potassium channels Kv3.1b/3.2 was unchanged. A significant decline of GAD-67, but not GAD-65, mRNA expressing neurons was observed in layer VI in animals older than P60. This suggested that subtle deficits in inhibition and enhanced excitation evoke the interneuronal changes in the synRastransgenic mouse cortex.
synRas 转基因小鼠在出生后的新皮质锥体神经元中表达组成型激活的 Valin12-Harvey Ras。这导致树突和棘突的体细胞肥大,棘突和突触密度增加,以及与谷氨酸受体介导的活性增加相关的突触长时程增强增强。不太清楚中间神经元如何对这些变化做出反应,这促使对中间神经元神经化学进行定量评估。然而,中间神经元很少表达转基因,但几种中间神经元类型表现出短暂的体细胞肥大。此外,NPY mRNA 的表达持续增加,标记神经元的层百分比也增加。钙蛋白酶和电压门控钾通道 Kv3.1b/3.2 的表达保持不变。在年龄超过 P60 的动物的 6 层中,观察到表达 GAD-67 的神经元,但不是 GAD-65 的 mRNA 显著减少。这表明抑制作用的细微缺陷和兴奋作用的增强会引发 synRas 转基因小鼠皮层中间神经元的变化。