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

中枢神经系统神经网络分析的转基因方法

• 批准号: 11670116
• 负责人: WATANABE Dai
• 金额: $ 2.3万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670116/
• 关键词: transgenic mouse; interneuron; glutamate; 小脳; GABA; イムノトキシン

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.

我们建立了在mGluR2启动子控制下表达人白细胞介素2受体α亚基与绿色荧光蛋白(GFP)融合的转基因小鼠。与mGluR2的表达一致，双重免疫染色显示GFP阳性细胞与胆碱乙酰转移酶(ChAT)免疫反应阳性的中间神经元在纹状体和视网膜中完全重叠。1.用免疫毒素介导的细胞靶向(IMCT)方法研究纹状体胆碱能中间神经元的生理作用。单侧胆碱能细胞消融引起急性转弯行为异常。这些小鼠表现为逐渐恢复，但由于过度刺激和抑制多巴胺作用而表现出异常转向。在急性期，刺激和抑制纹状体黑质神经元和抑制纹状体苍白质神经元可使基底节功能进入过度活跃状态。然后，D1和D2多巴胺受体被下调，缓解了以多巴胺为主的突触扰动，但在控制多巴胺反应方面留下了缺陷。2.视网膜神经节细胞反应的方向性选择性代表了一种在视网膜神经回路内工作的原始模式识别。通过使用LMCT选择性地消除视网膜胆碱能中间神经元，即星爆细胞，研究了方向选择性的细胞来源和机制。在成人视网膜中，星爆细胞消融不仅消除了神经节细胞反应的方向选择性，而且消除了由刺激运动产生的视动眼反射。因此，星状爆发细胞是通过整合突触传递来辨别刺激运动方向的关键因素，在稳定图像运动的信息处理中起着关键作用。

项目成果

Kazumichi Yoshida et.al.: "A Key Role of Starburst Amacrine Cells in Originating Retinal Directional Selectivity and Optokinetic Eye Movement"Neuron. 30. 771-780 (2001)

Kazumichi Yoshida 等人：“星爆无长突细胞在起源视网膜定向选择性和视动眼运动中的关键作用”神经元。

Satoshi Kaneko,Takatoshi Hikida,Dai Watanabe,Hiroshi Ichinose,Toshiharu Nagatsu,Robert J.Kreitman,Ira Pastan and Shigetada Nakanishi: "Synaptic Integration Mediated by Striatal Cholinergic Interneurons in Basal Ganglia"Science. 289. 633-637 (2000)

Satoshi Kaneko、Takatoshi Hikida、Dai Watanabe、Hiroshi Ichinose、Toshiharu Nagatsu、Robert J.Kreitman、Ira Pastan 和 Shigetada Nakanishi：“基底神经节纹状体胆碱能中间神经元介导的突触整合”科学。

Satoshi Kaneko, Takatoshi Hikida, Dai Watanabe, Hiroshi Ichinose, toshiharu Nagatsu, Robert J.Kreitman, Ira Pastan and Shigetada Nakanishi: "Synaptic Integration Mediated by Striatal Cholinergic Interneurons in Basal Ganglia"Science. vol.289. 633-637 (200

Satoshi Kaneko、Takatoshi Hikida、Dai Watanabe、Hiroshi Ichinose、toshiharu Nagatsu、Robert J.Kreitman、Ira Pastan 和 Shigetada Nakanishi：“基底神经节纹状体胆碱能中间神经元介导的突触整合”科学。

Kazumichi Yoshida,Dai Watanabe,Hiroshi Ishikane,Masao Tachibana,Ira Pastan and Shigetada Nakanishi: "A Key Role of Starburst Amacrine Cells in Originating Retinal Directional Selectivity and Optokinetic Eye Movement"Neuron. (in press).

Kazumichi Yoshida、Dai Watanabe、Hiroshi Ishikane、Masao Tachibana、Ira Pastan 和 Shigetada Nakanishi：“星爆无长突细胞在起源视网膜定向选择性和视动眼运动中的关键作用”神经元。

Kazumichi Yoshida, Dai Watanabe, Hiroshi Ishikane, Masao Tachibana, Ira Pastan and Shigetada Nakanishi: "A Key Role of Starburst Amacrine Cells in Originating Retinal Directional Selectivity and Optokinetic Eye Movement"Neuron. vol.30. 771-780 (2001)

Kazumichi Yoshida、Dai Watanabe、Hiroshi Ishikane、Masao Tachibana、Ira Pastan 和 Shigetada Nakanishi：“星爆无长突细胞在起源视网膜定向选择性和视动眼运动中的关键作用”神经元。