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首页> 外文期刊>Neuron >Conditional Deletion of All Neurexins Defines Diversity of Essential Synaptic Organizer Functions for Neurexins
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Conditional Deletion of All Neurexins Defines Diversity of Essential Synaptic Organizer Functions for Neurexins

机译:所有Neurexins的条件缺失定义了Neurexins的必需突触组织器功能的多样性

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摘要

Neurexins are recognized as key organizers of synapses that are essential for normal brain function. However, it is unclear whether neurexins are fundamental building blocks of all synapses with similar overall functions or context-dependent specifiers of synapse properties. To address this question, we produced triple cKO (conditional knockout) mice that allow ablating all neurexin expression in mice. Using neuron-specific manipulations combined with immunocytochemistry, paired recordings, and two-photon Ca2+ imaging, we analyzed excitatory synapses formed by climbing fibers on Purkinje cells in cerebellum and inhibitory synapses formed by parvalbumin-or somatostatin-positive interneurons on pyramidal layer 5 neurons in the medial prefrontal cortex. After pan-neurexin deletions, we observed in these synapses severe but dramatically different synaptic phenotypes that ranged from major impairments in their distribution and function (climbing-fiber synapses) to large decreases in synapse numbers (parvalbumin-positive synapses) and severe alterations in action potential-induced presynaptic Ca2+ transients (somatostatin-positive synapses). Thus, neurexins function primarily as context-dependent specifiers of synapses.
机译:Neurexins被认为是对正常脑功能至关重要的突触关键组织者。但是,目前尚不清楚Neurexins是否是所有突触的所有突触的基本构建块,或突触属性的相似函数或上下文依赖的说明符。为了解决这个问题,我们制作了三重CPO(条件淘汰)小鼠,允许在小鼠中烧蚀所有Neurexin表达。使用与免疫细胞化学,配对录制和双光子CA2 +成像结合的神经元定性操作,我们分析了通过攀爬纤维在小脑蛋白和生长抑制蛋白阳性间在金字塔蛋白层5神经元中形成的腓骨细胞上爬纤维组成的兴奋性突触内侧前额叶皮质。在Pan-Neurexin缺失后,我们在这些突触中观察到严重但显着不同的突触表型,这些表型在其分布和功能(爬光纤维突触)中的主要损伤范围内突触(Parvalbumin-ideri突触)(Parvalbumum-idsid突触)和严重改变的行动变动潜在诱导的突触前CA2 +瞬变(生长抑制素阳性突触)。因此,Neurexins主要函数作为突触的上下文依赖性说明符。

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  • 来源
    《Neuron》 |2017年第3期|共19页
  • 作者单位

    Stanford Univ Sch Med Dept Mol &

    Cellular Physiol 265 Campus Dr Stanford CA 94305 USA;

    Stanford Univ Sch Med Dept Mol &

    Cellular Physiol 265 Campus Dr Stanford CA 94305 USA;

    Stanford Univ Sch Med Dept Mol &

    Cellular Physiol 265 Campus Dr Stanford CA 94305 USA;

    Stanford Univ Sch Med Dept Mol &

    Cellular Physiol 265 Campus Dr Stanford CA 94305 USA;

    Stanford Univ Sch Med Dept Mol &

    Cellular Physiol 265 Campus Dr Stanford CA 94305 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
  • 关键词

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