Vargo J M, Marshall J F
Department of Psychobiology, University of California, Irvine 92717-4550, USA.
Neuroscience. 1997 Feb;76(4):1083-95. doi: 10.1016/s0306-4522(96)00414-9.
Unilateral ablation of medial agranular cortex in rats results in neglect of contralateral stimuli and reductions in amphetamine-induced expression of the immediate early gene, c-fos, in both caudate-putamen and globus pallidus. Both unilateral neglect and the reductions in dopamine agonist induction of subcortical Fos immunoreactivity dissipate over a matter of weeks. Dopamine agonism induces Fos predominantly in striatonigral cells and in globus pallidus via striatopallidal disinhibition, whereas Fos is induced in striatopallidal cells by administration of antagonists of the D2 dopamine receptor subfamily. To examine more directly effects of cortical injury on striatopallidal function, induction of striatal Fos by the D2 antagonist eticlopride (0.1 mg/kg, s.c.) was examined in rats with medial agranular cortex ablation. In the same animals, eticlopride-induced Fos in globus pallidus was also examined. Five days after unilateral cortex injury, in rats showing neglect, the numbers of Fos immunoreactive nuclei induced by eticlopride were reduced by 50% in caudate-putamen and 25% in globus pallidus of the ipsilateral hemisphere. These lesion effects were restricted to dorsolateral caudate-putamen and dorsal pallidum. Three or more weeks after cortical injury, in rats recovered from neglect, eticlopride-induced Fos was normalized in caudate-putamen, but still decreased by 20% in globus pallidus. Along with previous findings, these results suggest that behavioral recovery from neglect produced by cortical injury may be at least partially mediated by normalizations of function of both striatopallidal and striatonigral neurons. In addition, the present findings suggest that normalization of function of pallidal cells activated by eticlopride is not necessary for behavioral recovery from frontal cortex ablation. Lingering reductions in excitatory cortico-subthalamo-pallidal input may be responsible for the longer-lasting dysfunctions of these pallidal cells.
大鼠单侧损毁内侧无颗粒皮质会导致对侧刺激忽视，以及尾状核 - 壳核和苍白球中苯丙胺诱导的即刻早期基因c - fos表达减少。单侧忽视以及多巴胺激动剂诱导的皮质下Fos免疫反应性降低在数周内逐渐消失。多巴胺激动剂主要通过纹状体苍白球去抑制作用在纹状体黑质细胞和苍白球中诱导Fos，而D2多巴胺受体亚家族拮抗剂给药则在纹状体苍白球细胞中诱导Fos。为了更直接地研究皮质损伤对纹状体苍白球功能的影响，在损毁内侧无颗粒皮质的大鼠中检测了D2拮抗剂依替必利（0.1mg/kg，皮下注射）诱导的纹状体Fos。在同一动物中，还检测了依替必利诱导的苍白球Fos。单侧皮质损伤5天后，在出现忽视的大鼠中，依替必利诱导的Fos免疫反应性细胞核数量在同侧半球的尾状核 - 壳核中减少了50%，在苍白球中减少了25%。这些损伤效应局限于背外侧尾状核 - 壳核和背侧苍白球。皮质损伤3周或更长时间后，在从忽视中恢复的大鼠中，依替必利诱导的Fos在尾状核 - 壳核中恢复正常，但在苍白球中仍降低20%。与先前的研究结果一起，这些结果表明，皮质损伤所致忽视行为的恢复可能至少部分是由纹状体苍白球和纹状体黑质神经元功能的正常化介导的。此外，目前的研究结果表明，依替必利激活的苍白球细胞功能正常化对于额叶皮质损毁后的行为恢复并非必要。兴奋性皮质 - 丘脑底核 - 苍白球输入的持续减少可能是这些苍白球细胞功能障碍持续时间较长的原因。
