Failure of averaging in the construction of a conductance-based neuron model
Abstract
Parameters for models of biological systems are often obtained by averaging over experimental results from a number of different preparations. To explore the validity of this procedure, we studied the behavior of a conductance-based model neuron with five voltage-dependent conductances. We randomly varied the maximal conductance of each of the active currents in the model and identified sets of maximal conductances that generate bursting neurons that fire a single action potential at the peak of a slow membrane potential depolarization. A model constructed using the means of the maximal conductances of this population is not itself a one-spike burster, but rather fires three action potentials per burst. Averaging fails because the maximal conductances of the population of one-spike bursters lie in a highly concave region of parameter space that does not contain its mean. This demonstrates that averages over multiple samples can fail to characterize a system whose behavior depends on interactions involving a number of highly variable components.
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The 2-7 fold variations in mRNA expression are captured in computational models with degenerate solutions.
“and this is captured in computational models with degenerate solutions [18,31-34]”
From A feature and not a bug: Replication failures can lead to new biology (2026) · cites this paper as [33]
A consequence of degenerate systems is that averaging across individual samples may give results that differ from the behavior of all of the measurements that were used to calculate the means.
“A consequence of degenerate systems is that averaging across individual samples may give results that differ from the behavior of all of the measurements that were used to calculate the means [33].”
From A feature and not a bug: Replication failures can lead to new biology (2026) · cites this paper as [33]
A population of single-spike bursting models has similar waveforms but different underlying conductances.
“Figure 3 shows data from a population of single-spike bursting models with similar waveforms but different underlying conductances.”
From A feature and not a bug: Replication failures can lead to new biology (2026) · cites this paper as [33]
When a model is built from the mean Na+ conductance and mean K+ conductance from single-spike bursters, the model does not display the phenotype of the individual neurons whose data were used to calculate the means.
“When a model is built from the mean Na + conductance and mean K + conductance from these single-spike bursters, the model does not display the phenotype of the individual neurons whose data were used to calculate the means.”
From A feature and not a bug: Replication failures can lead to new biology (2026) · cites this paper as [33]
Whether averaging fails depends on the specifics of the compensations and correlations among the components that can give rise to similar waveforms or outputs.
“This need not occur, but depends on the specifics of the compensations and correlations among the components that can give rise to the similar waveforms or outputs [33].”
From A feature and not a bug: Replication failures can lead to new biology (2026) · cites this paper as [33]
Degeneracy can be produced in models with the same types of currents, but different numbers of channels, variable sets of voltage dependences of channels, or as a function of other parameters controlling channel function.
“Degeneracy can be produced in models with the same types of currents, but different numbers of channels [32,33], variable sets of voltage dependences of channels [35-37], or as a function of other parameters controlling channel function.”
From A feature and not a bug: Replication failures can lead to new biology (2026) · cites this paper as [33]
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Self-citation
- Authors
- Golowasch, J., Goldman, M. S., Abbott, L. F., & Marder, E.
- Affiliations
- Brandeis University (US)
- Harvard University (US)
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 2002-02-01
- Volume
- 87
- Issue
- 2
- Pages
- 1129-1131
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- OpenAlex
- W1820338024
- Cited by
- 290
- References
- 0
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 13 · 2023: 14 · 2022: 18 · 2021: 17 · 2020: 13 · 2019: 12 · 2018: 16 · 2017: 11 · 2016: 16 · 2015: 12 · 2014: 14 · 2013: 11 · 2012: 16
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurophysiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH 46742)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › stochastic dynamics and bifurcation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- conductance-based neuron model, maximal conductance, bursting neurons, parameter space, voltage-dependent conductance, action potential firing
- MeSH terms
- Action Potentials, Animals, Brachyura, Models, Neurological, Neurons, Potassium, Ganglia, Invertebrate
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