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PLoS Comput Biol. 2014 Nov 13;10(11):e1003949. doi: 10.1371/journal.pcbi.1003949. eCollection 2014 Nov.

A statistical method of identifying interactions in neuron-glia systems based on functional multicell Ca2+ imaging.

Author information

1
Integrated Systems Biology Laboratory, Graduate School of Informatics, Kyoto University, Sakyo-ku, Kyoto, Japan.
2
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; Center for Information and Neural Networks, Suita City, Osaka, Japan.
3
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Abstract

Crosstalk between neurons and glia may constitute a significant part of information processing in the brain. We present a novel method of statistically identifying interactions in a neuron-glia network. We attempted to identify neuron-glia interactions from neuronal and glial activities via maximum-a-posteriori (MAP)-based parameter estimation by developing a generalized linear model (GLM) of a neuron-glia network. The interactions in our interest included functional connectivity and response functions. We evaluated the cross-validated likelihood of GLMs that resulted from the addition or removal of connections to confirm the existence of specific neuron-to-glia or glia-to-neuron connections. We only accepted addition or removal when the modification improved the cross-validated likelihood. We applied the method to a high-throughput, multicellular in vitro Ca2+ imaging dataset obtained from the CA3 region of a rat hippocampus, and then evaluated the reliability of connectivity estimates using a statistical test based on a surrogate method. Our findings based on the estimated connectivity were in good agreement with currently available physiological knowledge, suggesting our method can elucidate undiscovered functions of neuron-glia systems.

PMID:
25393874
PMCID:
PMC4230777
DOI:
10.1371/journal.pcbi.1003949
[Indexed for MEDLINE]
Free PMC Article

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