Modeling the functional network of primary intercellular Ca2+ wave propagation in astrocytes and its application to study drug effects

JOURNAL OF THEORETICAL BIOLOGY

卷:356

Article

Pires, Marcelo^1,2  Raischel, Frank^1,3  Vaz, Sandra H.^4,5  Cruz-Silva, Andreia^4,5  Sebastiao, Ana M.^4,5  Lind, Pedro G.^1,6 

[1] Univ Lisbon, Fac Ciencias, Ctr Fis Teor & Computac, P-1649003 Lisbon, Portugal

[2] Univ Fed Amapa, Dept Fis, BR-68903419 Macapa, AP, Brazil

[3] Univ Lisbon, Inst Dom Luiz, Ctr Geofis, P-1749016 Lisbon, Portugal

[4] Univ Lisbon, Fac Med, Inst Farmacol & Neurociencias, P-1649028 Lisbon, Portugal

[5] Univ Lisbon, Inst Med Mol, Unidade Neurociencias, P-1649028 Lisbon, Portugal

[6] Carl von Ossietzky Univ Oldenburg, Inst Phys & ForWind, DE-26111 Oldenburg, Germany

关键词: Signal propagation;    Cellular tissues;    Complex networks;    Drug tests;   

DOI  :  10.1016/j.jtbi.2014.04.024

来源: Elsevier

【 摘 要 】

We introduce a simple procedure of multivariate signal analysis to uncover the functional connectivity among cells composing a living tissue and describe how to apply it for extracting insight on the effect of drugs in the tissue. The procedure is based on the covariance matrix of time resolved activity signals. By determining the time-lag that maximizes covariance, one derives the weight of the corresponding connection between cells. Introducing simple constraints, it is possible to conclude whether pairs of cells are functionally connected and in which direction. After testing the method against synthetic data we apply it to study intercellular propagation of Ca2+ waves in astrocytes following an external stimulus, with the aim of uncovering the functional cellular connectivity network. Our method proves to be particularly suited for this type of networking signal propagation where signals are pulse-like and have short time-delays, and is shown to be superior to standard methods, namely a multivariate Granger algorithm. Finally, based on the statistical analysis of the connection weight distribution, we propose simple measures for assessing the impact of drugs on the functional connectivity between cells. (C) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

Free