摘要星形膠質細胞中的大部分Ca2+活性在空間上僅限于微區(qū)，并發(fā)生在形成復雜解剖網狀結構的細小突起中，即所謂的海綿狀結構域。越來越多的文獻表明，這些星形細胞Ca2+信號可以影響神經元突觸的活動，從而調節(jié)通過神經元回路的信息流。局限于獲取所涉及的小空間尺度方面存在技術困難，關于星形膠質細胞形態(tài)對Ca2+微區(qū)活性的作用仍然知之甚少。本研究使用計算機技術和基于最近的超分辨率顯微鏡數據的細小突起的理想化3D 幾何形狀來研究星形膠質細胞納米級形態(tài)與局部Ca2+活性之間的關聯(lián)機制。模擬表明，星形細胞突起的納米形態(tài)強有力地塑造了Ca2+信號的時空特性并促進了局部Ca2+活性。該模型預測，這種效應在星形膠質細胞腫脹時會減弱，這是腦部疾病的標志，并在低滲透條件下通過實驗證實了這一點。該模型還預測，在重復的神經遞質釋放事件后，腫脹會阻礙星形膠質細胞的信號傳播?？偠灾?，三聯(lián)突觸中星形膠質細胞的突起與突觸前和突觸后結構密切接觸；本研究強調了星形膠質細胞在納米尺度上的復雜形態(tài)及其在病理條件下的重塑對所謂的三聯(lián)突觸的神經元-星形膠質細胞通訊的影響。

關鍵詞鈣微區(qū)；計算神經科學；細胞內信號傳導；納米形態(tài)；反應-擴散模擬

中圖分類號R741；R741.02文獻標識碼ADOI10.16780/j.cnki.sjssgncj.2022.10.020

Control of Ca2+signals by astrocyte nanoscale morphology at tripartite synapses

Audrey Denizot1,Misa Arizono2,3,4,U Valentin N?gerl2,3,Hugues Berry5,6,Erik De Schutter1

1.Computational Neuroscience Unit,Okinawa Institute of Science and Technology,Onna-Son,Japan.
2.Interdisciplinary Institute for Neuroscience,Université de Bordeaux,Bordeaux,France.
3.Interdisciplinary Institute for Neuroscience,CNRS UMR 5297,Bordeaux,France.
4.Department of Pharmacology,Kyoto University Graduate School of Medicine,Kyoto,Japan.
5.LIRIS,UMR5205 CNRS,Univ Lyon,Villeurbanne,France.
6.INRIA,Villeurbanne,France.

摘自Glia. 2022 Dec,70(12):2378-2391.doi:10.1002/glia.24258.Epub 2022 Sep 13.

AbstractMuch of the Ca2+activity in astrocytes is spatially restricted to microdomains and occurs in fine processes that form a complex anatomical meshwork, the so-called spongiform domain.A growing body of literature indicates that those astrocytic Ca2+signals can influence the activity of neuronal synapses and thus tune the flow of information through neuronal circuits. Because of technical difficulties in accessing the small spatial scale involved, the role of astrocyte morphology on Ca2+microdomain activity remains poorly understood. Here, we use computational tools and idealized 3D geometries of fine processes based on recent super-resolution microscopy data to investigate the mechanistic link between astrocytic nanoscale morphology and local Ca2+activity. Simulations demonstrate that the nano-morphology of astrocytic processes powerfully shapes the spatio-temporal properties of Ca2+signals and promotes local Ca2+activity. The model predicts that this effect is attenuated upon astrocytic swelling, hallmark of brain diseases, which we confirm experimentally in hypo-osmotic conditions. Upon repeated neurotransmitter release events,the model predicts that swelling hinders astrocytic signal propagation.Overall,this study highlights the influence of the complex morphology of astrocytes at the nanoscale and its remodeling in pathological conditions on neuron-astrocyte communication at so-called tripartite synapses, where astrocytic processes come into close contact with pre-and postsynaptic structures.

Key wordscalcium microdomains; computational neuroscience; intracellular signaling; nano-morphology; reaction-diffusion simulations