Activation of GluN2D-containing NMDA receptors promotes development of axons and axon-carrying dendrites of cortical interneurons.

IF 2.9 2区 医学 Q2 NEUROSCIENCES
Ina Köhler, Lisa-Marie Rennau, Leon Hoffmann, Ekaterina Demianchuk, Michelle Kaczmarski, Eric Sobierajski, Christian Riedel, Petra Wahle
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引用次数: 0

Abstract

GluN2D-containing NMDA receptors are expressed in early postnatal interneurons, but their role is enigmatic. We tested whether treatment with the GluN2C/D positive allosteric modulator CIQ and non-competitive antagonist DQP-1105 from days in vitro (DIV) 5-10 and DIV 15-20 modulates neurite growth in organotypic cultures. Calcium imaging confirmed a functional expression of GluN2D in nonpyramidal neurons. DQP treatment enhanced apical dendritic branching and increased ERK1/2 phosphorylation and spine density, suggesting a disinhibitory effect mirrored by a reduced expression of GAD-65, VGAT, and Syt-2. Control basket cells had larger axon-carrying dendrites (AcDs), and under CIQ, the AcDs grew even larger. The axons of CIQ-treated basket cells formed more branches within the dendritic field, and the effect was strongest for axons emerging from AcDs. DQP-treated basket cells also displayed more complex AcDs, presumably driven by enhanced network activity. However, local branching of basket cell axons was reduced under DQP in somatic axon cells but at control level in AcD cells. This suggested a growth-promoting effect of the enhanced network activity and that the AcD configuration neutralized the inhibitory action of DQP on basket cell axons. The results suggest a specific role of GluN2D signaling for development and remodeling of interneuronal axons.

含有glun2d的NMDA受体的激活促进皮层中间神经元轴突和轴突携带树突的发育。
含有glun2d的NMDA受体在出生后早期的中间神经元中表达,但其作用尚不清楚。我们测试了GluN2C/D阳性变构调节剂CIQ和非竞争拮抗剂DQP-1105在体外(DIV) 5-10和DIV 15-20中治疗是否能调节器官型培养中的神经突生长。钙成像证实GluN2D在非锥体神经元中有功能性表达。DQP处理增强了根尖树突分支,增加了ERK1/2磷酸化和脊柱密度,表明通过降低GAD-65、VGAT和Syt-2的表达反映了去抑制作用。对照篮细胞具有较大的轴突携带树突(AcDs),在CIQ作用下,AcDs更大。经ciq处理的篮状细胞的轴突在树突场内形成了更多的分支,对AcDs产生的轴突的影响最大。dqp处理的篮状细胞也显示出更复杂的AcDs,可能是由增强的网络活性驱动的。在DQP作用下,篮状细胞轴突局部分支减少,而在AcD细胞中则处于控制水平。这表明增强的网络活性具有促进生长的作用,并且AcD结构中和了DQP对篮细胞轴突的抑制作用。结果表明GluN2D信号在神经元间轴突的发育和重塑中具有特定的作用。
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来源期刊
Cerebral cortex
Cerebral cortex 医学-神经科学
CiteScore
6.30
自引率
8.10%
发文量
510
审稿时长
2 months
期刊介绍: Cerebral Cortex publishes papers on the development, organization, plasticity, and function of the cerebral cortex, including the hippocampus. Studies with clear relevance to the cerebral cortex, such as the thalamocortical relationship or cortico-subcortical interactions, are also included. The journal is multidisciplinary and covers the large variety of modern neurobiological and neuropsychological techniques, including anatomy, biochemistry, molecular neurobiology, electrophysiology, behavior, artificial intelligence, and theoretical modeling. In addition to research articles, special features such as brief reviews, book reviews, and commentaries are included.
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