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早期德雷珀介导的果蝇触角叶中神经毡结构和突触数量的胶质细胞精细化过程。

Early Draper-mediated glial refinement of neuropil architecture and synapse number in the Drosophila antennal lobe.

作者信息

Jindal Darren A, Leier Hans C, Salazar Gabriela, Foden Alexander J, Seitz Elizabeth A, Wilkov Abigail J, Coutinho-Budd Jaeda C, Broihier Heather T

机构信息

Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH, United States.

Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, United States.

出版信息

Front Cell Neurosci. 2023 Jun 2;17:1166199. doi: 10.3389/fncel.2023.1166199. eCollection 2023.

Abstract

Glial phagocytic activity refines connectivity, though molecular mechanisms regulating this exquisitely sensitive process are incompletely defined. We developed the Drosophila antennal lobe as a model for identifying molecular mechanisms underlying glial refinement of neural circuits in the absence of injury. Antennal lobe organization is stereotyped and characterized by individual glomeruli comprised of unique olfactory receptor neuronal (ORN) populations. The antennal lobe interacts extensively with two glial subtypes: ensheathing glia wrap individual glomeruli, while astrocytes ramify considerably within them. Phagocytic roles for glia in the uninjured antennal lobe are largely unknown. Thus, we tested whether Draper regulates ORN terminal arbor size, shape, or presynaptic content in two representative glomeruli: VC1 and VM7. We find that glial Draper limits the size of individual glomeruli and restrains their presynaptic content. Moreover, glial refinement is apparent in young adults, a period of rapid terminal arbor and synapse growth, indicating that synapse addition and elimination occur simultaneously. Draper has been shown to be expressed in ensheathing glia; unexpectedly, we find it expressed at high levels in late pupal antennal lobe astrocytes. Surprisingly, Draper plays differential roles in ensheathing glia and astrocytes in VC1 and VM7. In VC1, ensheathing glial Draper plays a more significant role in shaping glomerular size and presynaptic content; while in VM7, astrocytic Draper plays the larger role. Together, these data indicate that astrocytes and ensheathing glia employ Draper to refine circuitry in the antennal lobe before the terminal arbors reach their mature form and argue for local heterogeneity of neuron-glia interactions.

摘要

神经胶质细胞的吞噬活动可优化神经连接,不过调控这一极其敏感过程的分子机制尚未完全明确。我们将果蝇的触角叶作为模型,用以识别在无损伤情况下神经胶质细胞对神经回路进行优化的分子机制。触角叶的组织结构是固定的,其特征是由独特的嗅觉受体神经元(ORN)群体组成的各个神经小球。触角叶与两种神经胶质细胞亚型广泛相互作用:被鞘神经胶质细胞包裹着各个神经小球,而星形胶质细胞则在其中大量分支。在未受损的触角叶中,神经胶质细胞的吞噬作用在很大程度上尚不明确。因此,我们测试了Draper是否会调节两个具有代表性的神经小球(VC1和VM7)中ORN终末树突的大小、形状或突触前成分。我们发现,神经胶质细胞中的Draper会限制单个神经小球的大小,并抑制其突触前成分。此外,在年轻成虫期(这是终末树突和突触快速生长的时期),神经胶质细胞的优化作用很明显,这表明突触的添加和消除是同时发生的。已有研究表明Draper在被鞘神经胶质细胞中表达;出乎意料的是,我们发现它在蛹后期的触角叶星形胶质细胞中高水平表达。令人惊讶的是,Draper在VC1和VM7的被鞘神经胶质细胞和星形胶质细胞中发挥着不同的作用。在VC1中,被鞘神经胶质细胞中的Draper在塑造神经小球大小和突触前成分方面发挥着更重要的作用;而在VM7中,星形胶质细胞中的Draper发挥着更大的作用。总之,这些数据表明,在终末树突达到成熟形态之前,星形胶质细胞和被鞘神经胶质细胞利用Draper来优化触角叶中的神经回路,并支持神经元与神经胶质细胞相互作用存在局部异质性的观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ef6/10272751/1f37ab622394/fncel-17-1166199-g001.jpg

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