Effects of neural precursor lineage on pyramidal neuron function and morphology

描述（由申请人提供）：大脑皮层的兴奋性神经元是由一组不同的神经前体在产前产生的，其中一些是最近才发现的。放射状胶质干细胞（RGCs）直接产生神经元，至少有三种独立的中间神经前体细胞（IPCs），它们本身由RGCs产生，也产生神经元。有趣的是，每个皮质层内的神经元来源于这些不同的亲本细胞。为什么新皮层需要如此多的单个前体细胞类型，以及每层神经元的不同血统是否在新皮层回路中发挥功能作用，这些都尚未确定。在包括脆性X染色体和唐氏综合症在内的几种发育障碍中，IPCs的数量被认为是异常的。在这个项目中，我们用新的遗传命运定位工具确定了新皮质锥体神经元的特定谱系，并利用膜片钳电生理学和高分辨率3D成像确定了它们的结构、功能和连接特征。我们的初步数据表明，来自单个前体谱系的神经元，即使在同一层内，也具有特定的功能特性，因此多个IPC组直接构成了新皮层神经元和电路复杂性的基础。形态学和电生理参数将使用多学科方法和两个实验室合作进行定量检查。

DESCRIPTION (provided by applicant): Excitatory neurons of the cerebral cortex are generated prenatally from a diverse group of neural precursors, some of which have only been identified recently. Radial glia stem cells (RGCs) generate neurons directly and at least three separate lineages of Intermediate Neural Precursor Cells (IPCs), which are themselves produced from RGC, also produce neurons. Intriguingly, neurons within each cortical lamina are derived from these different parent cells. The reason why the neocortex requires so many individual precursor cell types, and whether the diverse ancestry of neurons within each layer plays a functional role in neocortical circuitry, has not been established. The numbers of IPCs are thought to be abnormal in several developmental disabilities, including Fragile X and Down's syndromes. In this project, we identify specific lineages of neocortical pyramidal neurons with novel genetic fate mapping tools and determine their structural, functional and connectional characteristics with patch clamp electrophysiology and high resolution 3D imaging. Our preliminary data indicate that neurons from individual precursor lineages, even within the same lamina, are imparted with specific functional properties and that the multiple IPC groups therefore directly underlie neuron and circuit complexity in the neocortex. Morphological and electrophysiological parameters will be quantitatively examined using a multidisciplinary approach and a two-laboratory collaboration.