TY - JOUR
T1 - Modeling sources of interlaboratory variability in electrophysiological properties of mammalian neurons
AU - Tebaykin, Dmitry
AU - Tripathy, Shreejoy J.
AU - Binnion, Nathalie
AU - Li, Brenna
AU - Gerkin, Richard
AU - Pavlidis, Paul
N1 - Funding Information:
This work is supported by a NeuroDevNet grant (to P. Pavlidis), a University of British Columbia bioinformatics graduate training program grant (to D. Tebaykin), a Canadian Institutes of Health Research postdoctoral fellowship (to S. J. Tripathy), National Sciences and Engineering Research Council of Canada Discovery Grant RGPIN-2016-05991, National Institutes of Health (NIH) Grants MH106674 and EB021711 (to R. C. Gerkin), and NIH Grants MH111099 and GM076990 (to P. Pavlidis).
Publisher Copyright:
© 2018 the American Physiological Society. All rights reserved.
PY - 2018/4
Y1 - 2018/4
N2 - Patch-clamp electrophysiology is widely used to characterize neuronal electrical phenotypes. However, there are no standard experimental conditions for in vitro whole cell patch-clamp electrophysiology, complicating direct comparisons between data sets. In this study, we sought to understand how basic experimental conditions differ among laboratories and how these differences might impact measurements of electrophysiological parameters. We curated the compositions of external bath solutions (artificial cerebrospinal fluid), internal pipette solutions, and other methodological details such as animal strain and age from 509 published neurophysiology articles studying rodent neurons. We found that very few articles used the exact same experimental solutions as any other, and some solution differences stem from recipe inheritance from advisor to advisee as well as changing trends over the years. Next, we used statistical models to understand how the use of different experimental conditions impacts downstream electrophysiological measurements such as resting potential and action potential width. Although these experimental condition features could explain up to 43% of the study-to-study variance in electrophysiological parameters, the majority of the variability was left unexplained. Our results suggest that there are likely additional experimental factors that contribute to cross-laboratory electrophysiological variability, and identifying and addressing these will be important to future efforts to assemble consensus descriptions of neurophysiological phenotypes for mammalian cell types. NEW & NOTEWORTHY This article describes how using different experimental methods during patch-clamp electrophysiology impacts downstream physiological measurements. We characterized how methodologies and experimental solutions differ across articles. We found that differences in methods can explain some, but not all, of the study-to-study variance in electrophysiological measurements. Explicitly accounting for methodological differences using statistical models can help correct downstream electrophysiological measurements for cross-laboratory methodology differences.
AB - Patch-clamp electrophysiology is widely used to characterize neuronal electrical phenotypes. However, there are no standard experimental conditions for in vitro whole cell patch-clamp electrophysiology, complicating direct comparisons between data sets. In this study, we sought to understand how basic experimental conditions differ among laboratories and how these differences might impact measurements of electrophysiological parameters. We curated the compositions of external bath solutions (artificial cerebrospinal fluid), internal pipette solutions, and other methodological details such as animal strain and age from 509 published neurophysiology articles studying rodent neurons. We found that very few articles used the exact same experimental solutions as any other, and some solution differences stem from recipe inheritance from advisor to advisee as well as changing trends over the years. Next, we used statistical models to understand how the use of different experimental conditions impacts downstream electrophysiological measurements such as resting potential and action potential width. Although these experimental condition features could explain up to 43% of the study-to-study variance in electrophysiological parameters, the majority of the variability was left unexplained. Our results suggest that there are likely additional experimental factors that contribute to cross-laboratory electrophysiological variability, and identifying and addressing these will be important to future efforts to assemble consensus descriptions of neurophysiological phenotypes for mammalian cell types. NEW & NOTEWORTHY This article describes how using different experimental methods during patch-clamp electrophysiology impacts downstream physiological measurements. We characterized how methodologies and experimental solutions differ across articles. We found that differences in methods can explain some, but not all, of the study-to-study variance in electrophysiological measurements. Explicitly accounting for methodological differences using statistical models can help correct downstream electrophysiological measurements for cross-laboratory methodology differences.
KW - Chemical solutions
KW - Computational modeling
KW - Electrophysiology
KW - Experimental conditions
KW - Intrinsic physiology: meta-analysis
KW - Metadata
KW - Patch clamp
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U2 - 10.1152/jn.00604.2017
DO - 10.1152/jn.00604.2017
M3 - Article
C2 - 29357465
AN - SCOPUS:85045403343
SN - 0022-3077
VL - 119
SP - 1329
EP - 1339
JO - Journal of neurophysiology
JF - Journal of neurophysiology
IS - 4
ER -