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。使用免疫毒素介导的细胞靶向技术（IMCT）选择性地消除视网膜胆碱能中间神经元，即starburst细胞，研究了定向选择性的机理。视网膜中的Starburst细胞消融不仅消除了神经节细胞反应的定向选择性，而且还取消了刺激运动得出的光动量反射。因此，Starburst细胞是通过综合突触传播区分刺激运动方向的关键要素，并在稳定图像运动的信息处理中起关键作用。2。 IMCT研究了纹状体胆碱能中间神经元的身体作用。单侧胆碱能细胞消融导致急性异常转弯行为。这些小鼠表现出等级效率，但由于过量刺激和对多巴胺作用的抑制而表现出异常转向。在急性期，分别通过刺激和抑制纹状体和纹状体神经元的刺激和抑制，将基底神经节功能转移到了超隔离状态。然后将D1和D2多巴胺受体下调，从而缓解多巴胺 - 促进性突触扰动，但在控制多巴胺反应时留下了缺陷。3。长期暴露于可卡因会导致与可卡因增强和成瘾有关的长期行为变化。可卡因成瘾的重要神经元底物是伏拟核（NAC）。尽管NAC的神经回路受到其他几个神经递质的控制，但它们参与可卡因成瘾仍然难以捉摸。我们用IMCT从成年NAC中消融了胆碱能中间神经元，并检查了乙酰胆碱发射器在与可卡因增强和成瘾相关的适应性行为变化中的作用。在双侧胆碱能细胞释放的小鼠中，慢性可卡因给药引起了运动活性的显着和逐步增加。此外，与野生型同窝仔相比，这些小鼠具有较低剂量的可卡因，表现出较低的可卡因。这项投资表明，NAC中的乙酰胆碱在可卡因的作用中起关键作用。较少的

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