The functional analysis of interneurons in central nervus system.

中枢神经系统中间神经元的功能分析。

• 批准号: 12680774
• 负责人: WATANABE Dai
• 金额: $ 2.5万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680774/
• 关键词: interneuron; transgenic mouse; immunotoxin; glutamute receptor; adenovirus vector; 受容体

1. The cellular origin and mechanism of directional selectivity were investigated by selectively eliminating retinal cholinergic interneurons, namely starburst cells, using the immunotoxin-mediated cell targeting techniques (IMCT). Starburst cell ablation in the 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.2. The physiological role of striatal cholinergic interneurons was investigated with IMCT. Unilateral cholinergic cell ablation caused an acute abnormal turning behavior. These mice showed gradual ecovery but displayed abnormal turning by both excess stimulation and inhibition of dopamine actions. In the acute phase, basal ganglia function was shifted to a hyperactiv … More e 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.3. Chronic exposure to cocaine causes long-lasting behavioral changes associated with cocaine reinforcement and addiction. An important neural substrate for cocaine addiction is the nucleus accumbens (Nac). Although the neural circuit of the Nac is controlled by several other neurotransmitters, their involvement in cocaine addiction remains elusive. We ablated cholinergic interneurons from the adult Nac with IMCT and examined the role of acetylcholine transmitter in adaptive behavioral changes associated with cocaine reinforcement and addiction. In bilaterally cholinergic cell-eliminated mice, chronic cocaine administration induced a prominent and progressive increase in locomotor activity. Moreover, these mice showed robust conditioned place preference with a lower dose of cocaine, compared with wild-type littermates. This investigation demonstrates that acetylcholine in the Nac plays a key role in actions of cocaine. Less

1.通过使用免疫毒素介导的细胞靶向技术（IMCT）选择性消除视网膜胆碱能中间神经元（即星爆细胞）来研究定向选择性的细胞起源和机制。视网膜中的星爆细胞消融不仅消除了神经节细胞反应的定向选择性。因此，由刺激运动产生的视动眼反射是通过综合突触传递来区分刺激运动方向的关键要素。 2．通过IMCT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导致小鼠出现急性异常转向行为。刺激和抑制多巴胺作用在急性期，基底神经节功能分别通过刺激和抑制纹状体黑质和纹状体苍白球神经元转变为过度活跃状态。 D1 和 D2 多巴胺受体随后下调，缓解了多巴胺主导的突触扰动，但在控制多巴胺反应方面留下了缺陷。 3. 长期接触可卡因会导致与可卡因强化和成瘾相关的长期行为变化。可卡因成瘾是伏隔核（Nac） 尽管Nac的神经回路是由其他几种神经递质控制的，但它们与可卡因成瘾的关系仍然难以捉摸。通过 IMCT 检测成年 Nac 的胆碱能中间神经元，并检查乙酰胆碱递质在与可卡因强化和成瘾相关的适应性行为变化中的作用。与野生型同窝小鼠相比，小鼠在使用较低剂量的可卡因时表现出强烈的条件性位置偏好。这项研究表明，Nac 中的乙酰胆碱在行动中发挥着关键作用。更少的可卡因。

项目成果

Satoshi Kaneko,Takatoshi Hikida,Dal 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、Dal 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。

Hazama, M., Watanabe, D., Suzuki, M., Mizoguchi, A., Pastan, I., Nakanishi, S.: "Different regulatory sequences are required for parvalbumin gene expression in skeltal muscles and neuronal cells of transgenic mice"Molecular Brain Research. (in press).

Hazama, M.、Watanabe, D.、Suzuki, M.、Mizoguchi, A.、Pastan, I.、Nakanishi, S.：“转基因小鼠骨骼肌和神经元细胞中的小清蛋白基因表达需要不同的调控序列”

Hazama, M., Watanabe, D., Suzuki, M., Mizoguchi, A., Pastan, I., Nakanishi, S.: "Differerent regulatory sequences are required for parvalbumi gere expression in skeltal muscles and neuronal cells of transgenic mice."Molecular Brain Research. (in press).

Hazama, M.、Watanabe, D.、Suzuki, M.、Mizoguchi, A.、Pastan, I.、Nakanishi, S.：“转基因小鼠骨骼肌和神经细胞中的 parvalbumi gere 表达需要不同的调控序列。

Kameko, S., Hikida, T., Watanabe, D., Ichinose, H., Nagatsu, T., Kreitman, R.J., Pastan, I., Nakanishi, S.: "Synaptic integration mediated by striatal cholinergic interneurons in basal ganglia function"Science. 289. 633-637 (2000)

Kameko, S.、Hikida, T.、Watanabe, D.、Ichinose, H.、Nagatsu, T.、Kreitman, R.J.、Pastan, I.、Nakanishi, S.：“基底神经节中纹状体胆碱能中间神经元介导的突触整合

Hikida, T., Kaneko, S., Isobe, T., Kitabatake, Y., Watanabe D., Pastan, I., and Nakanishi, S.: "Increased sensitivity to cocaine by cholinergic cell ablation nucleus accumbens."Proc Natl Acad Sci U S A. 98. 13351-13354 (2001)

Hikida, T.、Kaneko, S.、Isobe, T.、Kitabatake, Y.、Watanabe D.、Pastan, I. 和 Nakanishi, S.：“通过胆碱能细胞消融伏核增加对可卡因的敏感性。”Proc Natl