Modeling sources of interlaboratory variability in electrophysiological properties of mammalian neurons
Open accessAbstract
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.
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The field has not readily converged on a consensus number or definition of neuronal cell types.
“the field has not readily converged on a consensus number, or even definition, of neuronal cell types”
From Integrated Morphoelectric and Transcriptomic Classification of Cortical GABAergic Cells (2020) · cites this paper as Tebaykin et al., 2018
Different recording conditions and methods affect electrophysiological responses.
“different recording conditions and methods affect electrophysiological responses39–41”
From Classification of electrophysiological and morphological neuron types in the mouse visual cortex (2019) · cites this paper as [41]
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- Authors
- Tebaykin, D., Tripathy, S. J., Binnion, N., Li, B., Gerkin, R. C., & Pavlidis, P.
- Affiliations
- University of British Columbia (CA)
- Arizona State University (US)
- Corresponding author
- Tebaykin, Dmitry
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 2018-04-01
- Volume
- 119
- Issue
- 4
- Pages
- 1329-1339
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- PMC
- PMC5966732
- OpenAlex
- W2778526833
- Cited by
- 15
- References
- 41
- Citations by year
- 2025: 2 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 6 · 2018: 2
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurophysiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- UBC Bioinformatics graduate training program (N/A)
- CIHR post-doctoral fellowship (N/A)
- Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (RGPIN-2016-05991)
- HHS | National Institutes of Health (MH111099, GM076990)
- NeuroDevNet (N/A)
- HHS | NIH | National Institute of Mental Health (MH106674)
- HHS | NIH | National Institute of Biomedical Imaging and Bioengineering (EB021711)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- inter-laboratory variability, patch-clamp electrophysiology, artificial cerebrospinal fluid, experimental conditions, resting membrane potential, action potential width, methodological differences
- MeSH terms
- Animals, Mammals, Models, Theoretical, Neurons, Neurophysiology, Patch-Clamp Techniques, Electrophysiological Phenomena
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