STRIATAL NEUROANATOMY IN DOPAMINE TRANSPORTER KNOCKOUT MICE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 多巴胺是一种神经递质，与几种神经精神障碍的发病机制有关，例如帕金森病、精神分裂症、药物和酒精滥用、亨廷顿病和注意力缺陷多动障碍（ADHD）。 多巴胺转运体是一种膜结合蛋白，它将细胞外释放的多巴胺重新摄取回突触前神经末梢，是细胞外多巴胺水平的主要调节者。 缺乏多巴胺转运蛋白的小鼠在纹状体中具有持续升高的细胞外多巴胺浓度，纹状体是大脑中多巴胺能神经支配的主要靶区域。 除了表现出让人联想到慢性精神兴奋剂滥用和精神分裂症的行为症状外，这些小鼠还偶尔出现与类似亨廷顿氏病的纹状体神经变性相关的进行性运动障碍运动症状。 拟议的研究的目的是详细调查的后果持续hyperdopaminergia纹状体神经元解剖。 这将通过使用极高分辨率磁共振成像（MRI）（9.4 T）、常规免疫组织化学和超微结构成像模式（包括电子显微镜）采集和比较组织学数据来完成。 研究结果将有助于理解长期高纹状体多巴胺水平的影响，并可能导致更好地了解精神分裂症，药物成瘾和亨廷顿病的神经生物学。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dopamine is a neurotransmitter that has been implicated in the pathogenesis of several neuropsychiatric disorders, such as Parkinson's disease, schizophrenia, drug and alcohol abuse, Huntington's disease and attention-deficit hyperactivity disorder (ADHD). Dopamine transporter is a membrane-bound protein that reuptakes the released dopamine from the extracellular space back into presynaptic nerve terminals, and is the main regulator extracellular dopamine levels. Mice lacking the dopamine transporter have persistently elevated extracellular dopamine concentrations in the striatum, the main target region of dopaminergic innervation in the brain. In addition to displaying behavioral symptoms reminiscent of chronic psychostimulant abuse and schizophrenia, these mice sporadically develop progressive dyskinetic motor symptoms associated with striatal neurodegeneration resembling Huntingon's disease. The aim of the proposed studies is to investigate in detail the consequences of sustained hyperdopaminergia on striatal neuronal anatomy. This will be accomplished by acquiring and comparing histological data using very high resolution magnetic resonance imaging (MRI) (at 9.4 T), conventional immunohistochemistry, and ultrastructural imaging modalities including electron microscopy. The results will help to understand the effects of chronically high striatal dopamine levels, and may lead to better understanding of neurobiology of schizophrenia, drug addiction and Huntington's disease.