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GFP 转基因小鼠显示 Nav1.1 表达于新皮层锥体束投射神经元。

-GFP transgenic mouse revealed Nav1.1 expression in neocortical pyramidal tract projection neurons.

机构信息

Department of Neurodevelopmental Disorder Genetics, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Laboratory for Neurogenetics, RIKEN Center for Brain Science, Wako, Japan.

出版信息

Elife. 2023 May 23;12:e87495. doi: 10.7554/eLife.87495.

DOI:10.7554/eLife.87495
PMID:37219072
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10205085/
Abstract

Expressions of voltage-gated sodium channels Nav1.1 and Nav1.2, encoded by and genes, respectively, have been reported to be mutually exclusive in most brain regions. In juvenile and adult neocortex, Nav1.1 is predominantly expressed in inhibitory neurons while Nav1.2 is in excitatory neurons. Although a distinct subpopulation of layer V (L5) neocortical excitatory neurons were also reported to express Nav1.1, their nature has been uncharacterized. In hippocampus, Nav1.1 has been proposed to be expressed only in inhibitory neurons. By using newly generated transgenic mouse lines expressing promoter-driven green fluorescent protein (GFP), here we confirm the mutually exclusive expressions of Nav1.1 and Nav1.2 and the absence of Nav1.1 in hippocampal excitatory neurons. We also show that Nav1.1 is expressed in inhibitory and a subpopulation of excitatory neurons not only in L5 but all layers of neocortex. By using neocortical excitatory projection neuron markers including FEZF2 for L5 pyramidal tract (PT) and TBR1 for layer VI (L6) cortico-thalamic (CT) projection neurons, we further show that most L5 PT neurons and a minor subpopulation of layer II/III (L2/3) cortico-cortical (CC) neurons express Nav1.1 while the majority of L6 CT, L5/6 cortico-striatal (CS), and L2/3 CC neurons express Nav1.2. These observations now contribute to the elucidation of pathological neural circuits for diseases such as epilepsies and neurodevelopmental disorders caused by and mutations.

摘要

电压门控钠离子通道 Nav1.1 和 Nav1.2 的表达分别由 和 基因编码,据报道在大多数脑区这两种通道是相互排斥的。在幼年和成年新皮质中,Nav1.1 主要在抑制性神经元中表达,而 Nav1.2 则在兴奋性神经元中表达。尽管也报道了一小部分 V 层(L5)新皮质兴奋性神经元表达 Nav1.1,但它们的性质尚未确定。在海马体中,Nav1.1 被认为仅在抑制性神经元中表达。通过使用新生成的表达 启动子驱动的绿色荧光蛋白(GFP)的转基因小鼠系,我们在这里证实了 Nav1.1 和 Nav1.2 的相互排斥表达以及 Nav1.1 在海马体兴奋性神经元中的缺失。我们还表明,Nav1.1 不仅在 L5 而且在新皮质的所有层中表达于抑制性和一部分兴奋性神经元中。通过使用包括 L5 锥体束(PT)的 FEZF2 和 L6 皮质丘脑(CT)投射神经元的 TBR1 等新皮质兴奋性投射神经元标记物,我们进一步表明,大多数 L5 PT 神经元和一小部分 L2/3 皮质皮质(CC)神经元表达 Nav1.1,而大多数 L6 CT、L5/6 皮质纹状体(CS)和 L2/3 CC 神经元表达 Nav1.2。这些观察结果现在有助于阐明由 和 突变引起的癫痫和神经发育障碍等疾病的病理性神经回路。

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