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.

我们产生了转基因小鼠，表达人白细胞介素-2受体α亚基融合绿色荧光蛋白（GFP）的mGluR 2启动子的控制下。与mGluR 2的特异性表达一致，免疫双染显示纹状体和视网膜中的胆碱乙酰转移酶（ChAT）免疫反应阳性中间神经元与GFP阳性细胞完全重叠。1.采用免疫毒素介导的细胞靶向（IMCT）技术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异常转向行为。这些小鼠表现出逐渐恢复，但表现出异常转向过度刺激和抑制多巴胺的行动。在急性期，基底神经节的功能转移到一个过度活跃的状态，分别通过刺激和抑制纹状体黑质和striatopallidal神经元。然后D1和D2多巴胺受体下调，缓解多巴胺主导的突触扰动，但留下了控制多巴胺反应的缺陷。乙酰胆碱-多巴胺相互作用是基底神经节突触整合的协调和适应性调节。2.视网膜神经节细胞反应的方向选择性代表了视网膜神经回路中的一种原始模式识别。用lMCT选择性地清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起源和机制，成年视网膜星爆细胞消融不仅消除了神经节细胞反应的方向选择性，而且消除了刺激运动引起的视动性眼反射。因此，星爆细胞是通过整合性突触传递辨别刺激运动方向的关键元件，并在稳定图像运动的信息处理中发挥关键作用。

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。