Transgenic approach for the analysis of neural network in central nervus system

我们在mGluR2启动子的控制下产生了表达人白细胞介素-2受体α亚基融合绿色荧光蛋白（GFP）的转基因小鼠。与mGluR2特异性表达一致，双重免疫染色显示纹状体和视网膜中gfp阳性细胞与胆碱乙酰转移酶（ChAT）免疫反应性中间神经元完全重叠。采用免疫毒素介导的细胞靶向（IMCT）技术研究纹状体胆碱能间神经元的生理作用。单侧胆碱能细胞消融引起急性异常转向行为。这些小鼠表现出逐渐恢复，但在多巴胺作用的过度刺激和抑制下表现出异常的转向。在急性期，分别通过刺激和抑制纹状体神经元和纹状顶神经元，基底神经节功能转变为过度活跃状态。D1和D2多巴胺受体随后下调，缓解多巴胺主导的突触扰动，但在控制多巴胺反应方面留下缺陷。乙酰胆碱-多巴胺的相互作用在基底节区突触整合中受到协调和自适应调节。视网膜神经节细胞反应的定向选择性代表了在视网膜神经回路中操作的原始模式识别。通过lMCT选择性去除视网膜胆碱能中间神经元即星爆细胞，研究了定向选择性的细胞来源和机制。星爆细胞消融不仅破坏了神经节细胞反应的定向选择性，而且破坏了刺激运动引起的眼动反射。因此，星爆细胞是通过综合突触传递辨别刺激运动方向的关键因素，并在稳定图像运动的信息处理中发挥关键作用。

We generated transgenic mice that expressed human interleukin-2 receptor alpha subunit fused to green fluorescent protein(GFP)under the control of the mGluR2 promoter. Consistent with specific mGluR2 expression, double immunostaining showed the complete overlap of GFP-positive cells with choline acetyltransferase(ChAT)-immunoreactive interneurons in both striatum and retina.1.The physiological role of striatal cholinergic intemeurons was investigated with immunotoxin-mediated cell targeting(IMCT). Unilateral cholinergic cell ablation caused an acute abnormal turning behavior. These mice showed gradual recovery but displayed abnormal turning by both excess stimulation and inhibition of dopamine actions. In the acute phase, basal ganglia function was shifted to a hyperactive state by stimulation and suppression of striatonigral and striatopallidal neurons, respectively. D1 and D2 dopamine receptors were then down-regulated, relieving dopamine-predominant synaptic perturbation but leaving a defect in controlling dopamine responses. The acetylcholine-dopamine interaction is concertedly and adaptively regulated for basal ganglia synaptic integration.2.The directional selectivity of retinal ganglion cell responses represents a primitive pattern recognition that operates within a retinal neural circuit. The cellular origin and mechanism of directional selectivity were investigated by selectively eliminating retinal cholinergic interneurons, namely starburst cells, using lMCT.Starburst cell ablation in the adult retina abolished not only directional selectivity of ganglion cell responses but also an optokinetic eye reflex derived by stimulus movement. Starburst cells therefore serve as the key element that discriminates the direction of stimulus movement through integrative synaptic transmission and play a pivotal role in information processing that stabilizes image motion.