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小鼠海马区中间神经元多样性的时空起源蓝图。

A blueprint for the spatiotemporal origins of mouse hippocampal interneuron diversity.

机构信息

Program in Developmental Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.

出版信息

J Neurosci. 2011 Jul 27;31(30):10948-70. doi: 10.1523/JNEUROSCI.0323-11.2011.

Abstract

Although vastly outnumbered, inhibitory interneurons critically pace and synchronize excitatory principal cell populations to coordinate cortical information processing. Precision in this control relies upon a remarkable diversity of interneurons primarily determined during embryogenesis by genetic restriction of neuronal potential at the progenitor stage. Like their neocortical counterparts, hippocampal interneurons arise from medial and caudal ganglionic eminence (MGE and CGE) precursors. However, while studies of the early specification of neocortical interneurons are rapidly advancing, similar lineage analyses of hippocampal interneurons have lagged. A "hippocampocentric" investigation is necessary as several hippocampal interneuron subtypes remain poorly represented in the neocortical literature. Thus, we investigated the spatiotemporal origins of hippocampal interneurons using transgenic mice that specifically report MGE- and CGE-derived interneurons either constitutively or inducibly. We found that hippocampal interneurons are produced in two neurogenic waves between E9-E12 and E12-E16 from MGE and CGE, respectively, and invade the hippocampus by E14. In the mature hippocampus, CGE-derived interneurons primarily localize to superficial layers in strata lacunosum moleculare and deep radiatum, while MGE-derived interneurons readily populate all layers with preference for strata pyramidale and oriens. Combined molecular, anatomical, and electrophysiological interrogation of MGE/CGE-derived interneurons revealed that MGE produces parvalbumin-, somatostatin-, and nitric oxide synthase-expressing interneurons including fast-spiking basket, bistratified, axo-axonic, oriens-lacunosum moleculare, neurogliaform, and ivy cells. In contrast, CGE-derived interneurons contain cholecystokinin, calretinin, vasoactive intestinal peptide, and reelin including non-fast-spiking basket, Schaffer collateral-associated, mossy fiber-associated, trilaminar, and additional neurogliaform cells. Our findings provide a basic blueprint of the developmental origins of hippocampal interneuron diversity.

摘要

尽管数量上远远超过兴奋性主细胞群体,但抑制性中间神经元对于协调皮质信息处理至关重要,它们通过在祖细胞阶段限制神经元的潜能来精确控制。这种控制的精确性依赖于中间神经元的显著多样性,这些多样性主要在胚胎发生过程中由遗传决定。与它们的新皮质对应物一样,海马中间神经元起源于内侧和尾状神经节隆起(MGE 和 CGE)前体。然而,虽然新皮质中间神经元早期特化的研究正在迅速推进,但海马中间神经元的类似谱系分析却滞后了。由于几种海马中间神经元亚型在新皮质文献中仍然代表性不足,因此进行“海马中心”的研究是必要的。因此,我们使用专门报告 MGE 和 CGE 衍生中间神经元的转基因小鼠,来研究海马中间神经元的时空起源。我们发现,海马中间神经元分别在 E9-E12 和 E12-E16 期间从 MGE 和 CGE 产生两个神经发生波,并在 E14 时侵入海马体。在成熟的海马体中,CGE 衍生的中间神经元主要定位于颗粒层分子层和深放射层的浅层,而 MGE 衍生的中间神经元则容易在所有层中定植,偏爱锥体细胞层和始层。对 MGE/CGE 衍生中间神经元进行的分子、解剖和电生理联合研究表明,MGE 产生表达 parvalbumin、somatostatin 和 nitric oxide synthase 的中间神经元,包括快速放电 basket、双分层、轴突-轴突、始层-颗粒层分子层、神经胶质形成细胞和常春藤细胞。相比之下,CGE 衍生的中间神经元包含胆囊收缩素、钙结合蛋白、血管活性肠肽和 reelin,包括非快速放电 basket、Schaffer 侧支相关、苔藓纤维相关、三层和其他神经胶质形成细胞。我们的发现为海马中间神经元多样性的发育起源提供了一个基本蓝图。

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