Regional and Genetic Diversity of Cortical Interneurons

描述（由申请人提供）：项目总结：中间神经元对高级皮质处理至关重要，相反，这些细胞的功能障碍在临床上被认为是癫痫、舞蹈病和运动障碍的原因。最近的工作已经确定，皮质中间神经元主要或完全来自端脑的subpallial部分。使用一种新的移植方法，我们最近的命运映射尾侧与内侧神经节隆起的E13.5小鼠大脑。虽然我们发现这两个区域都是皮质中间神经元的来源，但源自这两个隆起的细胞的层状分布、平铺和形态是不同的。我们已经开始表征中间神经元起源于这两个隆起的基础上，其诱发的放电模式，免疫标记物和形态。特别是，我们希望评估是否来自这些结构的中间神经元的变化，随着发展的进展。此外，我们建议扩展这项研究的遗传命运映射是否特定的发育表达的bHLH和同源结构域转录因子的祖细胞，产生特定的亚类皮质中间神经元的表达。因此，这一建议将提供第一个全面的分析皮层中间神经元多样性的发育起源。

DESCRIPTION (provided by applicant): Project Summary: Interneurons are critical to higher cortical processing and conversely malfunction of these cells is clinically implicated as a cause of epilepsy, chorea and dyskinesia. Recent work has determined that cortical interneurons are largely or completely derived from the subpallial portion of the telencephalon. Using a novel transplantation approach, we have recently fate mapped the caudal versus the medial ganglionic eminences of the E13.5 mouse brain. While we find that both these regions are sources of cortical interneurons, the laminar distribution, tiling and morphology of cells originating from these 2 eminences are distinct. We have begun to characterize interneurons originating from these 2 eminences on the basis of their evoked firing pattern, immunological markers and morphology. In particular we wish to assess whether the interneurons that are derived from these structures changes as development progresses. In addition, we propose to extend this study by genetically fate mapping whether specific developmental expressed bHLH and homeodomain transcription factors are expressed in progenitors that give rise to specific subclasses of cortical interneurons. This proposal will therefore provide the first comprehensive analysis of the developmental origins of cortical interneuron diversity.