Behavioral and physiological roles of the striatal GABAergic interneuronal types

纹状体 GABA 能中间神经元类型的行为和生理作用

基本信息

批准号：
16300102
负责人：
KOBAYASHI Kazuto
金额：
$ 7.17万
依托单位：
Fukushima Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

The striatum is a central structure of the basal ganglia neural circuitry that mediates a variety of brain functions including motor control, motor learning, and reward-associated behavior. It contains some GABAergic interneuronal types that are different in their morphology and electrophysiological property. However, the difference in their behavioral and physiological roles remains unknown. In the present study, we addressed to study the roles of two kinds of straital GABAergic interneuronal types containing somatostatin (SST) or parvalbumin (PVA). We utilized immunotoxin cell targeting to eliminate the specific neuronal type from the neural circuitry and studied the resultant phenotypic changes. To eliminate the striatal GABAergic interneurons containing SST, we generated the mutant mice in which the human interleukin-2 receptor a-subunit (IL-2Rα) gene cassette was introduced into the mouse preprosomatostatin gene locus. These mice were injected intrastriatally with the recombinant immunotoxin, and the number of target neurons were reduced in the mutants. Phenotypic analysis of the mutants indicated that the SST-containing GABAergic interneurons play an important role in suppression of spontaneous motor behavior. In addition, to eliminate the straital GABAergic interneurons containing PVA we tried to produce the mutant mice in which the human IL-2Rα cassette was introduced into the mouse PVA gene locus. The knock-in targeting vector was introduced into embryonic stem (ES) cells, and the cells carrying the targeted mutation were screened with PCR and southern blot hybridization. We succeeded in obtaining multiple ES cells carrying the targeted mutation. Using these cells we are planning to generate the knock-in mutant mice and perform immunotoxin cell targeting to elucidate the behavioral and physiological roles of the striatal GABAergic interneurons containing PVA.

纹状体是基底神经节神经回路的中心结构，介导多种大脑功能，包括运动控制、运动学习和奖励相关行为，它包含一些形态和电生理特性不同的 GABA 能中间神经元类型。它们的行为和生理作用的差异仍然未知。在本研究中，我们致力于研究两种含有生长抑素（SST）或小白蛋白的海峡 GABA 能中间神经元类型的作用。 (PVA)。我们利用免疫毒素细胞靶向消除神经回路中的特定神经元类型，并研究由此产生的表型变化。为了消除含有 SST 的纹状体 GABA 能中间神经元，我们产生了人类白细胞介素 2 受体 a- 的突变小鼠。亚基（IL-2Rα）基因盒被引入小鼠前促生长素抑制素基因位点，这些小鼠被注射重组体。突变体的表型分析表明，含有 SST 的 GABA 能中间神经元在抑制自发运动行为中发挥着重要作用。此外，为了消除含有 PVA 的海峡 GABA 能中间神经元。尝试生产突变小鼠，其中将人IL-2Rα盒引入小鼠PVA基因位点，将敲入靶向载体引入胚胎干（ES）。细胞，并通过PCR和southern blot杂交筛选出携带靶向突变的细胞，我们计划利用这些细胞产生敲入突变小鼠并进行免疫毒素细胞靶向。阐明含有 PVA 的纹状体 GABA 能中间神经元的行为和生理作用。