A feature and not a bug: Replication failures can lead to new biology

Marder, Eve

doi:10.1016/j.conb.2026.103268

Cited by 0Philosophy and History of ScienceMeta-analysis and systematic reviewsInterdisciplinary Research and Collaboration

A feature and not a bug: Replication failures can lead to new biology

Open access

Marder, Eve·2026·Current Opinion in Neurobiology

DOI 10.1016/j.conb.2026.103268

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Abstract

Much attention has rightly been paid in recent years to the importance of rigorous experimental design and the use of appropriate statistics for data analysis. This is of tantamount importance in the evaluation of clinical trials and because new methods that generate large data sets may not be transparent without advanced analytical and statistical methods. Most findings in the biological literature are confirmed, either by the authors in the process of doing the work, or subsequently by the authors and others, who build on the findings. That said, it is also crucially important to recognize that failures to replicate are to be expected every so often, even when investigators are careful in studies of complex, degenerate, biological systems. Failures to replicate may not reflect issues with experimental design or interpretation, but may instead reveal new principles and provide important routes to new discoveries.

AI snapshot

Written from the paper’s full text.

TL;DR

Failures to replicate are often not misconduct or error but expected consequences of degenerate biological systems, environmental non-stationarity, and hidden differences in experimental conditions. Marder argues these failures can reveal new biology and should prompt rethinking of assumptions rather than dismissal.

Key findings

Degenerate systems can produce similar outputs with different underlying parameters: in a Morris–Lecar model, two versions with reversed Q10 values behave almost identically at 22°C but diverge at 7°C and 27°C, with one losing rhythmic activity and the other maintaining it.
Averaging across degenerate neurons can fail: averaging Na⁺ and K⁺ conductances from 150 single-spike bursting models produced a model that generated three spikes/burst rather than the single-spike phenotype of the individual cells.
In a seven-current model, two neurons with similar control bursting behaved differently when a Ca²⁺ conductance was reduced to 75%, became similar again at 50%, and diverged markedly at 25% and 0%, showing that apparent replication failures can depend on which perturbation is tested.
Environmental non-stationarity can cause replication failures: crab pyloric rhythm “crash” temperatures initially above 25–28°C later reached as high as 35°C, apparently tracking yearly fluctuations in mean ocean temperature.
Identified neurons across individuals can show 2–7 fold variation in mRNA expression of most cellular components, and “room temperature” can vary by 4–5°C, enough to alter biological processes.

Methods

This is a review/opinion synthesis, not a primary research study; the Data availability statement says “No data was used for the research described in the article.”
It draws on computational simulations (e.g., Morris–Lecar models, models with five or seven voltage-dependent currents) and cited experimental literature from the author’s and other laboratories.
The main analysis is conceptual: using examples of degeneracy, averaging failures, temperature sensitivity, and environmental change to reinterpret replication failures as potential sources of biological insight.

Limitations

The paper states that in experimental studies “one does not have access to all of the factors that contribute to an outcome,” making it difficult to predict which perturbations will reveal individual differences.
It notes that lack of environmental stationarity and changing human health/habits can contribute to replication failures that are hard to measure and evaluate.
The text makes evident that the argument relies on selected computational and experimental examples rather than a systematic review or new empirical data; the article itself reports no new data.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.conb.2026.103268

Cites

72 of 72 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

70 of 124 cited sources checked · 36 supported · 0 flagged · accuracy not yet measured

Premisecitation
§ Molecular and analysis tools, genetic strains, and preprint servers ensure that replication across the international scientific community occurs automatically
Other laboratories working on the same preparation also routinely perform the same baseline measurements.
“Other laboratories working on the same preparation also routinely perform the same baseline measurements [7][8][9][10][11][12].”
Quote in the paperSubstantial claim1 of 3 sources checked
- cites [7] Nusbaum, 2002, A small-systems approach to motor pattern generation, Nature source
- cites [8] Nusbaum, 2012, Neuropeptide modulation of microcircuits, Curr Opin Neurobiol source
  The Neuropeptide families and Modulating microcircuit organization and dynamics sections discuss experiments on stomatogastric circuits, but do not say that other laboratories routinely perform the same baseline measurements. Searches for “baseline” and for routine measurements by other laboratories found no passage addressing that practice. Page numbers were not available in our copy. (LLM, conf=0.74)
  Experimental — accuracy not yet measured
- cites [9] Nusbaum, 1999, The role of cotransmitters and peptidase activity in shaping the actions of peptidergic neurons, Soc Neurosci Abstr
  Not checked in the free run.
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
Similar physiological outputs can be produced by variable sets of component parameters.
“similar physiological outputs can be produced by variable sets of component parameters [17][18][19][20]”
Quote in the paperSubstantial claim3 of 4 sources checked
- cites [17] Swensen, 2005, Robustness of burst firing in dissociated purkinje neurons with acute or long-term reductions in sodium conductance, J Neurosci source
- cites [18] Prinz, 2004, Similar network activity from disparate circuit parameters, Nat Neurosci source
- cites [19] Xie, 2024, Similar excitability through different sodium channels and implications for the analgesic efficacy of selective drugs, eLife source
- cites [20] Reva, 2025, Higher-order interactions in neuronal function: from genes to ionic currents in biophysical models, Proc Natl Acad Sci U S A source
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
Genetically identical animals show different behaviors.
“and genetically identical animals show different behaviors.”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [21] Albantakis, 2019, Causal composition: structural differences among dynamically equivalent systems, Entropy source
  The Introduction describes analyses of small dynamical systems, and Discussion §4.2 discusses simulated agents and their behavior. Neither addresses whether genetically identical animals behave differently. Searches for the claim and for genetic identity and behavioral variation found no supporting passage in our copy. (LLM, conf=0.76)
  Experimental — accuracy not yet measured
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
In wild-type populations of animals with similar performance profiles, 2-7 fold variations in the mRNA expression of most cellular components are seen in identified neurons across individuals.
“In wild-type populations of animals with similar performance profiles, 2-7 fold variations in the mRNA expression of most cellular components are seen in identified neurons across individuals [25-30]”
Quote in the paperSubstantial claim5 of 6 sources checked
- cites [25] Schulz, 2006, Variable channel expression in identified single and electrically coupled neurons in different animals, Nat Neurosci source
- cites [26] Schulz, 2007, Quantitative expression profiling of identified neurons reveals cell-specific constraints on highly variable levels of gene expression, Proc Natl Acad Sci U S A source
  The Results report 3- to 5-fold variation in ion-channel mRNA among identified neurons of the same type, and the Discussion describes these neurons as maintaining constant network function. The paper measured six ion-channel genes in crab neurons; it does not establish a 2- to 7-fold range or extend the finding to most cellular components. No page number is available in our copy. (LLM, conf=0.88)
  Experimental — accuracy not yet measured
- cites [27] Schulz, 2017, Homeostatic plasticity of excitability in crustacean central pattern generator networks, Curr Opin Neurobiol source
  The ‘Plasticity of Channel mRNA Expression’ section discusses cell-specific variation and correlations in channel transcripts in identified stomatogastric neurons. The Conclusions also describe substantial variability in ionic conductances across animals. Neither passage establishes a 2–7-fold range for mRNA expression or says that it applies to most cellular components. (LLM, conf=0.82)
  Experimental — accuracy not yet measured
- cites [28] Northcutt, 2019, Molecular profiling of single neurons of known identity in two ganglia from the crab Cancer borealis, Proc Natl Acad Sci U S A source
  The Discussion (General Insights; page unavailable) says expression patterns vary within defined neuron types, supporting the general point that identified neurons need not have identical mRNA profiles. The paper does not establish a 2–7-fold range for most cellular components, or tie that range to wild-type animals with similar performance profiles. (LLM, conf=0.84)
  Experimental — accuracy not yet measured
- cites [29] Northcutt, 2016, Deep sequencing of transcriptomes from the nervous systems of two decapod crustaceans to characterize genes important for neural circuit function and modulation, BMC Genom source
  The Discussion discusses gene-expression differences across tissues and says this study provides a reference for subsequent expression analyses. Neither it nor the retrieved Results passages report 2–7-fold mRNA variation across individuals with similar performance profiles. Searches for that range and for variability in identified neurons found relevant titles in the References, but no passage in this paper stating the claimed finding. (LLM, conf=0.74)
  Experimental — accuracy not yet measured
- cites [30] Tobin, 2009, Correlations in ion channel mRNA in rhythmically active neurons, PLoS One source
  The Introduction describes variable ion-channel mRNA levels in identified neurons despite similar activity, and the Results report variation across cardiac-ganglion cells. But the paper measures eight ion-channel transcripts, not most cellular components; its reported range is 3–9 fold, not 2–7 fold. The cited passages do not establish the wild-type qualifier. (LLM, conf=0.88)
  Experimental — accuracy not yet measured
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
The lifetimes of brain proteins vary widely.
“Moreover, the lifetimes of brain proteins vary widely [22][23][24]”
Quote in the paperNot a substantial claim3 of 3 sources checked
- cites [22] Bulovaite, 2022, A brain atlas of synapse protein lifetime across the mouse lifespan, Neuron source
  The Abstract reports that PSD95 lifetimes at excitatory synapses across the mouse brain range from hours to several months. This supports wide variation in the lifetime of one brain protein across synapses, but does not establish that lifetimes vary widely among brain proteins generally. (LLM, conf=0.85)
  Experimental — accuracy not yet measured
- cites [23] Sorokina, 2026, Protein trafficking and synaptic demand configure complex and dynamic synaptome architectures of individual neurons, Sci Rep source
  The Introduction (page unavailable) says that synapse-protein turnover differs between synapses, and the Results section “PSD95 protein half-life varies with age” reports modeled PSD95 half-lives of 1.54 days in juvenile mice versus 4.3 days in mature mice. This supports variation in a brain protein’s lifetime, but the paper’s reported analysis focuses on PSD95 rather than establishing how widely lifetimes vary across brain proteins generally. (LLM, conf=0.82)
  Experimental — accuracy not yet measured
- cites [24] Heo, 2026, Sex- and experience-dependent regulation of synaptic protein turnover, Proc Natl Acad Sci U S A source

Premisecitation
§ Introduction
Underappreciated differences among study populations and environmental variables may still contribute to failures of replication.
“Additionally, underappreciated differences among study populations and environmental variables may still contribute to failures of replication [6].”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [6] Baker, 2026, The problem with one-size-fits-all medicine: biological sex and the aging immune system, PLoS Biol source
  In “Implications for research and medicine” (page unavailable), the paper says that failing to account for sex limits how findings can be generalized. Its Conclusions (page unavailable) say that culture conditions affect outcomes and that sex- and age-informed study designs make findings more reproducible. It does not directly state that differences among study populations and environmental variables cause failures of replication. (LLM, conf=0.76)
  Experimental — accuracy not yet measured
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
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]”
Quote in the paperNot a substantial claim2 of 5 sources checked
- cites [18] Prinz, 2004, Similar network activity from disparate circuit parameters, Nat Neurosci source
- cites [31] Dopp, 2026, Conductance relationships across compartments associated with bursting output in a model of a motor neuron in the crustacean cardiac ganglion, J Neurophysiol source
  The Introduction says computational models can produce similar activity from many different conductance parameter sets, supporting the point about degenerate solutions. It reports two- to six-fold variation in maximal conductances, not two- to seven-fold variation in mRNA expression, and does not say the models capture that mRNA range. (LLM, conf=0.85)
  Experimental — accuracy not yet measured
- cites [32] Goldman, 2001, Global structure, robustness, and modulation of neuronal models, J Neurosci source
- cites [33] Golowasch, 2002, Failure of averaging in the construction of a conductance-based neuron model, J Neurophysiol source
- cites [34] Prinz, 2017, Degeneracy rules, J Physiol source
  In the main text (p. 2409), Prinz describes computational models with several-fold variation in presynaptic parameters that nonetheless produce similar outputs, calling this parameter degeneracy. The passage does not establish that the models capture specifically 2–7-fold variation in mRNA expression. (LLM, conf=0.84)
  Experimental — accuracy not yet measured
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
Genetically identical animals become degenerate over time as stochastic molecular processes accrue differences.
“Even genetically identical animals become degenerate over time, as stochastic molecular and processes accrue differences over time [21]”
Quote in the paperNot a substantial claim1 of 1 sources checked
- cites [21] Albantakis, 2019, Causal composition: structural differences among dynamically equivalent systems, Entropy source
  The Introduction and Methods discuss causal composition in small dynamical systems, not genetically identical animals. Searches for genetically identical animals, stochastic molecular processes, and degeneration over time found no passage addressing the claim. (LLM, conf=0.76)
  Experimental — accuracy not yet measured
Interpretationcitation
§ Conclusions
Because of degenerate systems and the lack of stationarity in our world, it is most difficult to achieve standards of reliability in exactly those circumstances in which it is most critical for public policy or decision-making.
“Unfortunately, because of degenerate systems and the lack of stationarity in our world, it is most difficult to achieve standards of reliability in exactly those circumstances in which it is most critical for public policy or decision-making [72,73].”
Quote in the paperNot a substantial claim1 of 2 sources checked
- cites [72] Sisodiya, 2024, Hot brain: practical climate change advice for neurologists, Pract Neurol source
  The Practical actions section says existing data can conflict and that older studies may reflect climate conditions already surpassed. But neither that passage nor the additional searches for degenerate systems, stationarity, reliability, and decision-making addresses the claimed difficulty of meeting reliability standards when policy decisions are most critical. (LLM, conf=0.74)
  Experimental — accuracy not yet measured
- cites [73] Sisodiya, 2024, Climate change and disorders of the nervous system, Lancet Neurol source
Findingcitation
§ Lack of stationarity in the environment and subject populations can produce failures to replicate
In initial studies of the effects of temperature on the pyloric rhythm of crabs, the rhythm increased in frequency in a permissive range, but then crashed or lost function at temperatures above 25-28°C.
“In our initial studies of the effects of temperature on the pyloric rhythm of crabs, we found that the rhythm increased in frequency in a permissive range, but then 'crashed' or lost function at temperatures above 25-28 • C [41, 65,66].”
Quote in the paperSubstantial claim3 of 3 sources checked
- cites [41] Tang, 2010, Precise temperature compensation of phase in a rhythmic motor pattern, PLoS Biol source
  The Results section, “Effects of Temperature on the Pyloric Rhythm” (page unavailable), reports that the crab pyloric rhythm increased about fourfold in frequency as temperature rose from 7°C to 23°C. It does not report a crash or loss of function above 25–28°C; the biological recordings described here stop at 23°C. (LLM, conf=0.88)
  Experimental — accuracy not yet measured
- cites [65] Soofi, 2014, Phase maintenance in a rhythmic motor pattern during temperature changes in vivo, J Neurophysiol source
  The Results report that pyloric frequency increased as temperature rose from 11°C to 26°C and that motor patterns became more disrupted at higher temperatures. They do not establish that the rhythm generally crashed or lost function above 25–28°C: the experiments reached 26°C, and some animals retained regular bursts while others showed interruptions. The Discussion mentions LP-neuron failure approaching 27°C in prior in vitro work, not a general loss of the rhythm. (LLM, conf=0.87)
  Experimental — accuracy not yet measured
- cites [66] Tang, 2012, Robustness of a rhythmic circuit to short- and long-term temperature changes, J Neurosci source
  The Results (Temperature acclimation of the pyloric rhythm; page unavailable) show that frequency increased across the 7–23 °C permissive range. The Results (More extreme temperatures disrupt the pyloric rhythm; page unavailable) report disruption at 27 °C and a complete crash at 31 °C in one preparation, but do not establish 25–28 °C as a general crash threshold; the critical temperature varied among animals. (LLM, conf=0.84)
  Experimental — accuracy not yet measured
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
Model neuron A and model neuron B have the same constellation of ion channels, but with different values of their maximal conductances.
“Model neuron A and model neuron B have the same constellation of ion channels, but with different values of their maximal conductances.”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [42] Alonso, 2019, Visualization of currents in neural models with similar behavior and different conductance densities, eLife source
Findingcitation
§ Lack of stationarity in the environment and subject populations can produce failures to replicate
The crash temperatures changed yearly as the mean ocean temperatures fluctuated.
“Eventually it became clear that the crash temperatures changed yearly, as the mean ocean temperatures fluctuated [45].”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [45] Marder, 2021, From the neuroscience of individual variability to climate change, J Neurosci source
Premisecitation
§ Failure of averaging
A third confound can result from averaging across populations of seemingly similar individuals who nonetheless are different in one or more important characteristics.
“A third confound can result from averaging across populations of seemingly similar individuals who nonetheless are different in one or more important characteristics [6].”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [6] Baker, 2026, The problem with one-size-fits-all medicine: biological sex and the aging immune system, PLoS Biol source
Premisecitation
§ Conclusions
C. elegans pharyngeal pumping consists of myogenic plateau potentials which are driven by the nervous system.
“C. elegans pharyngeal pumping consists of myogenic plateau potentials which are driven by the nervous system.”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [47] Kenngott, 2025, An unusual potassium conductance protects Caenorhabditis elegans pharyngeal muscle rhythms against environmental noise, Proc Natl Acad Sci U S A source
Premisecitation
§ 54 *
Q10 varied with the voltage and temperature at which currents were measured.
“Some channel kinetics measured at low temperature were qualitatively different from measurements made close to physiological temperatures [55], and Q10 varied with the voltage and temperature at which currents were measured [55].”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [55] Ranjan, 2019, A kinetic map of the homomeric voltage-gated potassium channel (Kv) family, Front Cell Neurosci source
Premisecitation
§ Conclusions
Selectively blocking one of those Na(V) subtypes reduces nociceptor excitability only if the other subtypes are weakly expressed.
“Selectively blocking one of those Na(V) subtypes reduces nociceptor excitability only if the other subtypes are weakly expressed.”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [19] Xie, 2024, Similar excitability through different sodium channels and implications for the analgesic efficacy of selective drugs, eLife source
  The Abstract says that blocking NaV1.7 becomes inconsequential when other NaV subtypes are abundant enough to maintain nociceptor excitability. The Discussion gives the broader condition: blocking an isoform matters when excitability depends on it, with channel inactivation also affecting that dependence. Thus the claim captures the role of other subtypes but overstates weak expression as the sole requirement. (LLM, conf=0.81)
  Experimental — accuracy not yet measured
Premisecitation
§ Conclusions
In a homeostatistically regulated neuron in which maximal conductances and channel voltage-dependence are coordinately regulated, it is possible to study how the two mechanisms are called into action by repeated perturbations.
“In a homeostatistically regulated neuron in which maximal conductances and channel voltage-dependence are coordinately regulated, it is possible to study how the two mechanisms are called into action by repeated perturbations.”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [37] Mondal, 2026, Persistent adaptation through dual-timescale regulation of ion channel properties, Proc Natl Acad Sci U S A source
Interpretationcitation
§ 54 *
Measurements at 35 °C may vary considerably from those that were made at lower temperatures.
“Measurements at 35 • C may vary considerably from those that were made at lower temperatures.”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [55] Ranjan, 2019, A kinetic map of the homomeric voltage-gated potassium channel (Kv) family, Front Cell Neurosci source
Premisecitation
§ Studies at 'room temperature' can lead to 'failures to replicate'
Laboratory buildings display significant fluctuations in room temperature.
“Laboratory buildings display significant fluctuations in room temperature [51,52].”
Quote in the paperSubstantial claim1 of 2 sources checked
- cites [51] Kiani, 2025, Room temperature: understanding the importance and impact, J Phys Chem Biophys
  Not checked in the free run.
- cites [52] Beam, 1983, A quantitative study of potassium channel kinetics in rat skeletal muscle from 1 to 37 degrees C, J Gen Physiol source
  The paper’s opening passage describes controlled temperature experiments on potassium channels in rat skeletal muscle, not temperature conditions in laboratory buildings. A search for room-temperature fluctuations and ambient laboratory conditions found no passage addressing the claim. (LLM, conf=0.72)
  Experimental — accuracy not yet measured
Interpretationcitation
§ Conclusions
Modulation of voltage-dependence can contribute to resilience subsequent to perturbation.
“These studies demonstrate that modulation of voltage-dependence can both alter a neuron's activity and contribute to resilience subsequent to perturbation”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [35] Huang, 2026, Sensitivity of a model oscillator to shifts in the voltage-dependence of one or more ionic currents, J Neurophysiol source
Premiseown data
§ Degenerate, multiple solutions in neuronal behavior
Under 'control' conditions, the models are degenerate and show very similar bursting behavior.
“Despite this, under 'control' conditions, the models are degenerate and show very similar bursting behavior”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [42] Alonso, 2019, Visualization of currents in neural models with similar behavior and different conductance densities, eLife source
Interpretationcitation
§ Studies at 'room temperature' can lead to 'failures to replicate'
If experimental temperature is not carefully controlled and reported, experiments from different laboratories may be discrepant.
“If experimental temperature is not carefully controlled and reported [53], experiments from different laboratories may be discrepant”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [53] Teixeira da Silva, 2021, Room temperature in scientific protocols and experments should be defined: a reprodicibility issue, Biotechniques source
Premisecitation
§ 54 *
Many biological processes vary considerably over 4-5 °C, well within the range of what is normally considered room temperature.
“because many biological processes vary considerably over 4-5 • C [40,55-59], well within the range of what is normally considered room temperature.”
Quote in the paperSubstantial claim6 of 6 sources checked
- cites [40] Garrity, 2010, Running hot and cold: behavioral strategies, neural circuits, and the molecular machinery for thermotaxis in C. elegans and Drosophila, Genes Dev source
  In “A note on terminology,” the paper says biochemical processes are affected by temperature even within an animal’s normal thermal zone. “Thermosensory regulation of development” also says locomotion, metabolism, and life span are significantly affected by ambient temperature. Our copy does not establish that many processes vary considerably over a specifically 4–5°C range considered room temperature. (LLM, conf=0.82)
  Experimental — accuracy not yet measured
- cites [55] Ranjan, 2019, A kinetic map of the homomeric voltage-gated potassium channel (Kv) family, Front Cell Neurosci source
  The Results section (page not provided) reports substantial changes in Kv-channel kinetics across measurements at 15, 25, and 35°C, supporting temperature sensitivity. It does not establish that many biological processes vary considerably over a 4–5°C difference within the room-temperature range. (LLM, conf=0.85)
  Experimental — accuracy not yet measured
- cites [56] Goodman, 2018, The extraordinary AFD thermosensor of C. elegans, Pflugers Arch source
  The ‘Regulation of systemic temperature responses by AFD’ section says physiological and biochemical processes are temperature-sensitive, and ‘Thermosensory navigation behaviors’ describes a C. elegans behavior within roughly 2°C of either side of its prior temperature. The paper does not establish that many biological processes vary considerably across a 4–5°C range, or define that range as room temperature. Page numbers were not available in our copy. (LLM, conf=0.83)
  Experimental — accuracy not yet measured
- cites [57] Goodman, 2019, How Caenorhabditis elegans senses mechanical stress, temperature, and other physical Stimuli, Genetics source
  The Thermosensation section says temperature regulates biochemical reaction rates, and the Behavioral responses to thermal stimuli section describes changes in C. elegans behavior across differences of a few degrees (page numbers unavailable). These passages support temperature sensitivity, but do not establish that many biological processes vary considerably over specifically 4–5 °C or define that interval as room temperature. (LLM, conf=0.83)
  Experimental — accuracy not yet measured
- cites [58] Schapiro, 2024, Resilience of circuits to environmental challenge, Curr Opin Neurobiol source
  The Introduction section “Temperature and pH Change Dynamics of Neuronal and Circuit Function” (page unavailable) says temperature affects most biological molecules and that even very small changes can alter neuronal network behavior. It does not establish that many biological processes vary considerably over a 4–5 °C interval or discuss that interval as part of room temperature. (LLM, conf=0.86)
  Experimental — accuracy not yet measured
- cites [59] Schapiro, 2024, I(h) block reveals separation of timescales in pyloric rhythm response to temperature changes in Cancer borealis, eLife source
  The Results report that pyloric rhythm frequency increased with temperature, and the Temperature protocol describes measurements in 2°C steps from 11°C to 21°C (page not specified in our copy). This supports temperature sensitivity in one biological process, but not the broader claim about many processes or the characterization of a 4–5°C change as within room temperature. (LLM, conf=0.83)
  Experimental — accuracy not yet measured
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
In computational models it is feasible to examine the structures of the parameter spaces that contribute to an output or a physiological state.
“In computational models it is feasible to examine the structures of the parameter spaces that contribute to an output or a physiological state [31,42,46,47].”
Quote in the paperNot a substantial claim4 of 4 sources checked
- cites [31] Dopp, 2026, Conductance relationships across compartments associated with bursting output in a model of a motor neuron in the crustacean cardiac ganglion, J Neurophysiol source
- cites [42] Alonso, 2019, Visualization of currents in neural models with similar behavior and different conductance densities, eLife source
- cites [46] Alonso, 2023, Gating of homeostatic regulation of intrinsic excitability produces cryptic long-term storage of prior perturbations, Proc Natl Acad Sci U S A source
- cites [47] Kenngott, 2025, An unusual potassium conductance protects Caenorhabditis elegans pharyngeal muscle rhythms against environmental noise, Proc Natl Acad Sci U S A source
Interpretationcitation
§ Lack of stationarity in the environment and subject populations can produce failures to replicate
By monitoring ocean temperatures, it is possible to ask mechanistic questions about how nervous systems from wild-caught animals are altered by the environment.
“By monitoring the ocean temperatures, it is possible to ask mechanistic questions about how nervous systems from wild-caught animals are altered by the environment [67][68][69][70].”
Quote in the paperSubstantial claim4 of 4 sources checked
- cites [67] Jacquerie, 2026, Compensation of the effects of temperature on a motor system in the crab, Cancer borealis, bioRxiv source
  The Discussion (page unavailable) links seasonal ocean temperatures to questions about how the crab motor system maintains function and calls for mechanistic study of environmental change. But the Materials and methods (page unavailable) describe laboratory-acclimated crabs and controlled bath temperatures, not monitoring ocean temperatures to assess environmental effects on their nervous systems. (LLM, conf=0.83)
  Experimental — accuracy not yet measured
- cites [68] Jacquerie, 2026, Temperature and pH-dependent potassium currents of muscles of the stomatogastric nervous system of the crab, Cancer borealis, iScience source
  The Introduction (page unavailable) uses reported ocean-temperature variation to motivate a mechanistic study of temperature and pH effects on the crab stomatogastric nervous system and its muscles. But the Methods (page unavailable) describe commercially purchased crabs and controlled laboratory temperatures; the paper does not say it monitored the animals’ ocean temperatures or linked their environmental histories to nervous-system changes. (LLM, conf=0.78)
  Experimental — accuracy not yet measured
- cites [69] Tran, 2026, Quantitative neuropeptidomics reveals thermal acclimation-induced remodeling of peptidergic signaling in the American lobster Homarus americanus, bioRxiv source
  The Introduction says the study probes how temperature affects lobster neural systems, and Animals and Tissue Collection describes analysis of neural tissues after acclimation at three temperatures. But the researchers used controlled laboratory temperatures, not monitored ocean temperatures; that section says the lobsters were purchased commercially and does not establish that they were wild-caught. Our copy provides no page numbers for these passages. (LLM, conf=0.84)
  Experimental — accuracy not yet measured
- cites [70] Stein, 2023, Thermal acclimation and habitat-dependent differences in temperature robustness of a crustacean motor circuit, Front Cell Neurosci source
Premisecitation
§ 54 *
Some channel kinetics measured at low temperature were qualitatively different from measurements made close to physiological temperatures.
“Some channel kinetics measured at low temperature were qualitatively different from measurements made close to physiological temperatures [55], and Q10 varied with the voltage and temperature at which currents were measured [55].”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [55] Ranjan, 2019, A kinetic map of the homomeric voltage-gated potassium channel (Kv) family, Front Cell Neurosci source
Findingcitation
§ Lack of stationarity in the environment and subject populations can produce failures to replicate
Several years later, crab preparations retained robust pyloric rhythms at temperatures as high as 35°C.
“Several years later, preparations retained robust pyloric rhythms at temperatures as high as 35 • C [45].”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [45] Marder, 2021, From the neuroscience of individual variability to climate change, J Neurosci source
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
Biological systems that appear similar when unperturbed might respond to perturbations in unanticipated different ways.
“biological systems that appear similar when unperturbed might respond to perturbations in unanticipated different ways [43-45]”
Quote in the paperSubstantial claim3 of 3 sources checked
- cites [43] Alonso, 2020, Temperature compensation in a small rhythmic circuit, eLife source
- cites [44] Rue, 2022, Repeated applications of high potassium elicit long-term changes in a motor circuit from the crab, Cancer borealis, iScience source
- cites [45] Marder, 2021, From the neuroscience of individual variability to climate change, J Neurosci source
Premisecitation
§ Conclusions
Correlations that are present in biological data from the large cells are not necessary for model function.
“Interestingly, they demonstrate that correlations that are present in biological data from the large cells are not necessary for model function.”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [31] Dopp, 2026, Conductance relationships across compartments associated with bursting output in a model of a motor neuron in the crustacean cardiac ganglion, J Neurophysiol source
Findingcitation
§ Molecular and analysis tools, genetic strains, and preprint servers ensure that replication across the international scientific community occurs automatically
We recently compiled and directly compared similar data across investigators and laboratories and found essential concordance.
“We recently compiled and directly compared similar data across investigators and laboratories [13] and found essential concordance.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [13] Gorur-Shandilya, 2022, Mapping circuit dynamics during function and dysfunction, eLife source
  Checked before — its earlier verdict is held back until a new check runs.
Findingcitation
§ Degenerate, multiple solutions in neuronal behavior
When perturbed substantially, degenerate solutions respond differently.
“Nonetheless, this figure illustrates another feature of degenerate solutions; when perturbed substantially, they respond differently.”
- Also stated in: § Degenerate, multiple solutions in neuronal behavior · plain
  “In Figure 1, this is seen by the divergent behaviors of the models at temperatures other than 22 • C.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [38] Kenngott, 2026
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Interpretationreasoning
§ Introduction
Failures to replicate may provide important clues to what is missing in our understanding of the world.
“Failures to replicate may provide important clues to what is missing in our understanding of the world.”
Quote in the paperNot a substantial claim
- Rests on an assumption: Most failures to replicate have no malign etiology, but are a consequence of dedicated scientists working at the frontiers of knowledge.
- Rests on an assumption: Research practices are continuously evolving, and important errors are unlikely to go undiscovered for long.
- Rests on an assumption: Substantial differences in laboratory practices can inadvertently creep into study designs.
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
Biological systems are inherently degenerate.
“Biological systems are inherently degenerate [14-16]”
Quote in the paperSubstantial claim0 of 3 sources checked
- cites [14] Albantakis, 2024, The brain's best kept secret is its degenerate structure, J Neurosci source
  Checked before — its earlier verdict is held back until a new check runs.
- cites [15] Marom, 2023, A biophysical perspective on the resilience of neuronal excitability across time scales, Nat Rev Neurosci source
- cites [16] Yang, 2023, Homeostatic regulation of neuronal function: importance of degeneracy and pleiotropy, Front Cell Neurosci source
  Checked before — its earlier verdict is held back until a new check runs.
Interpretationreasoning
§ Degenerate, multiple solutions in neuronal behavior
The wide variation in lifetimes of brain proteins will enhance the diversity of solutions in single neurons, synapses, and circuits.
“and this will enhance the diversity of solutions in single neurons, synapses, and circuits.”
Quote in the paperNot a substantial claim
Interpretationreasoning
§ Molecular and analysis tools, genetic strains, and preprint servers ensure that replication across the international scientific community occurs automatically
As reagents and methods move freely in the international community, the baseline measurements that are needed to use these shared tools become checks and validators of data reliability.
“As reagents and methods move freely in the international community, the baseline measurements that are needed to use these shared tools become checks and validators of data reliability.”
Quote in the paperSubstantial claim
- Rests on an assumption: Labs working on worms, flies, mice, and rats routinely share reagents, methods, protocols, genetic strains, and regularly pool data.
Interpretationreasoning
§ Molecular and analysis tools, genetic strains, and preprint servers ensure that replication across the international scientific community occurs automatically
Consequently, as new methods are assimilated into the community, a great deal of automatic replication occurs as laboratories around the world do the baseline and control experiments needed to implement new protocols and reagents.
“Consequently, as new methods are assimilated into the community, a great deal of automatic replication occurs as laboratories around the world do the baseline and control experiments needed to implement new protocols and reagents.”
Quote in the paperSubstantial claim
- Rests on an assumption: Labs working on worms, flies, mice, and rats routinely share reagents, methods, protocols, genetic strains, and regularly pool data.
Interpretationreasoning
§ Molecular and analysis tools, genetic strains, and preprint servers ensure that replication across the international scientific community occurs automatically
Molecular and analysis tools, genetic strains, and preprint servers ensure that replication across the international scientific community occurs automatically.
“Molecular and analysis tools, genetic strains, and preprint servers ensure that replication across the international scientific community occurs automatically”
Quote in the paperSubstantial claim
- Rests on an assumption: It is becoming common for laboratories to post their 'completed' manuscripts on preprint servers such as BioRxiv.
- Rests on an assumption: These preprints can be easily updated and revised, and comments arising from the international community serve as an organic community selfcorrecting mechanism.
Interpretationreasoning
§ Degenerate, multiple solutions in neuronal behavior
Degeneracy can be seen at the single-cell level when examining the influence of channel function on neuronal excitability.
“Degeneracy can be seen at the single-cell level when examining the influence of channel function on neuronal excitability.”
Quote in the paperSubstantial claim
Premisecitation
§ Failure of averaging
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].”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [33] Golowasch, 2002, Failure of averaging in the construction of a conductance-based neuron model, J Neurophysiol source
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
At 25% and 0% deletion of one Ca2+ current, the two models behave markedly different.
“Nonetheless at 25% and 0% ,the two models behave markedly different.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [42] Alonso, 2019, Visualization of currents in neural models with similar behavior and different conductance densities, eLife source
  Checked before — its earlier verdict is held back until a new check runs.
Interpretationreasoning
§ Degenerate, multiple solutions in neuronal behavior
The variable responses of the two models are not 'noise', but are biological features that are not revealed until an appropriate perturbation is given.
“The variable responses of the two models are not 'noise', but are biological features that are not revealed until an appropriate perturbation is given.”
Quote in the paperSubstantial claim
- Rests on an assumption: The Morris-Lecar models are representative of biological neurons (or degenerate biological systems).
Premisecitation
§ Failure of averaging
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.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [33] Golowasch, 2002, Failure of averaging in the construction of a conductance-based neuron model, J Neurophysiol source
Interpretationcitation
§ Conclusions
Modulation of voltage-dependence can alter a neuron's activity.
“These studies demonstrate that modulation of voltage-dependence can both alter a neuron's activity and contribute to resilience subsequent to perturbation”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [35] Huang, 2026, Sensitivity of a model oscillator to shifts in the voltage-dependence of one or more ionic currents, J Neurophysiol source
  Checked before — its earlier verdict is held back until a new check runs.
Premisecitation
§ Failure of averaging
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].”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [33] Golowasch, 2002, Failure of averaging in the construction of a conductance-based neuron model, J Neurophysiol source
Premisecitation
§ 54 *
Ranjan et al. created a kinetic map of 40 homomeric K+ channels' function from 15 °C to 35 °C.
“In a remarkable study Ranjan et al. [55] created a kinetic map of 40 homomeric K + channels' function from 15 • C to 35 • C.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [55] Ranjan, 2019, A kinetic map of the homomeric voltage-gated potassium channel (Kv) family, Front Cell Neurosci source
  Checked before — its earlier verdict is held back until a new check runs.
Interpretationreasoning
§ Lack of stationarity in the environment and subject populations can produce failures to replicate
The slow increase in North Atlantic Ocean temperatures would cause slow acclimation that would alter the effects of acute temperature perturbations on the animals' nervous systems.
“In retrospect, we should not have been surprised that the slow increase in North Atlantic Ocean temperatures would cause slow acclimation that would alter the effects of acute temperature perturbations on the animals' nervous systems.”
Quote in the paperSubstantial claim
Premisecitation
§ Failure of averaging
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.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [33] Golowasch, 2002, Failure of averaging in the construction of a conductance-based neuron model, J Neurophysiol source
Interpretationreasoning
§ Conclusions
The mechanism is degenerate.
“This is a wonderful example of a degenerate mechanism with direct implications for clinical management of pain.”
Quote in the paperSubstantial claim
Interpretationreasoning
§ Studies at 'room temperature' can lead to 'failures to replicate'
Reporting study temperature as room temperature can be an example of groups intending to do the same experiment but not doing so.
“One disconcerting example of this can arise when study temperature is reported as room temperature (RT).”
Quote in the paperSubstantial claim
- Rests on an assumption: Failures to replicate can occur when two or more groups intend to do the 'same' experiment, but do not.
Interpretationreasoning
§ 54 *
The etiology of the failure to replicate remains unclear.
“The authors of this study argue that they saw no difference in their results at the two temperatures but do not show the data at the two temperatures, so the etiology of the failure to replicate remains unclear.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [54] Chen, 2026, A reassessment of NMDA receptor-dependent presynaptic homeostatic plasticity, Proc Natl Acad Sci U S A source
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
At 50% deletion of one Ca2+ current, the models are again degenerate and produce similar behavior.
“it is striking that at 50% deletion the models are again degenerate, and produce similar behavior.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [42] Alonso, 2019, Visualization of currents in neural models with similar behavior and different conductance densities, eLife source
  Checked before — its earlier verdict is held back until a new check runs.
Interpretationreasoning
§ Lack of stationarity in the environment and subject populations can produce failures to replicate
The lack of environmental stationarity likely involves many factors that contribute to failures to replicate that may be difficult to measure and evaluate.
“the lack of environmental stationarity likely involves many factors that contribute to failures to replicate that may be difficult to measure and evaluate.”
Quote in the paperNot a substantial claim
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
At 75% deletion of one Ca2+ current, the two models are noticeably different.
“Although the 75% panel is noticeably different in the two models”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [42] Alonso, 2019, Visualization of currents in neural models with similar behavior and different conductance densities, eLife source
  Checked before — its earlier verdict is held back until a new check runs.
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
Biological systems that appear similar when unperturbed may show hidden 'cryptic' changes that are variable but only revealed when perturbed.
“may show hidden 'cryptic' changes that are variable but only revealed when perturbed [44,45]”
Quote in the paperSubstantial claim0 of 2 sources checked
- cites [44] Rue, 2022, Repeated applications of high potassium elicit long-term changes in a motor circuit from the crab, Cancer borealis, iScience source
  Checked before — its earlier verdict is held back until a new check runs.
- cites [45] Marder, 2021, From the neuroscience of individual variability to climate change, J Neurosci source
  Checked before — its earlier verdict is held back until a new check runs.
Premisecitation
§ Conclusions
A similar shift in Na(V) dependence occurs in response to inflammation.
“A similar shift in Na(V) dependence occurs in in response to inflammation.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [19] Xie, 2024, Similar excitability through different sodium channels and implications for the analgesic efficacy of selective drugs, eLife source
  Checked before — its earlier verdict is held back until a new check runs.
Interpretationreasoning
§ Degenerate, multiple solutions in neuronal behavior
If one studied only the control and the 50% case, one would not suspect that the other cases would show different properties.
“If one studied only the control and the 50% case, one would not suspect that the other cases would show different properties.”
Quote in the paperSubstantial claim
Interpretationreasoning
§ Degenerate, multiple solutions in neuronal behavior
If both investigators had examined the full range of perturbations, they would have easily seen that the two models respond differently because of their different underlying parameter sets.
“If both investigators had examined the full range of perturbations, they would have easily seen that the two models respond differently because of their different underlying parameter sets.”
Quote in the paperSubstantial claim
Interpretationreasoning
§ Degenerate, multiple solutions in neuronal behavior
This simple example predicts that apparent failures to replicate will often appear in degenerate systems.
“This simple example predicts that apparent failures to replicate will often appear in degenerate systems.”
Quote in the paperSubstantial claim
- Rests on an assumption: The Morris-Lecar models are representative of biological neurons (or degenerate biological systems).
- Rests on an assumption: Degeneracy is common in biological systems.
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
Biological systems are degenerate.
“Because biological systems are degenerate”
Quote in the paperSubstantial claim0 of 3 sources checked
- cites [43] Alonso, 2020, Temperature compensation in a small rhythmic circuit, eLife source
  Checked before — its earlier verdict is held back until a new check runs.
- cites [44] Rue, 2022, Repeated applications of high potassium elicit long-term changes in a motor circuit from the crab, Cancer borealis, iScience source
  Checked before — its earlier verdict is held back until a new check runs.
- cites [45] Marder, 2021, From the neuroscience of individual variability to climate change, J Neurosci source
  Checked before — its earlier verdict is held back until a new check runs.
Premisecitation
§ Conclusions
An unusual, rapidly inactivating potassium conductance confers exceptional noise robustness on the system.
“In this computational model an unusual, rapidly inactivating potassium conductance confers exceptional noise robustness on the system.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [47] Kenngott, 2025, An unusual potassium conductance protects Caenorhabditis elegans pharyngeal muscle rhythms against environmental noise, Proc Natl Acad Sci U S A source
  Checked before — its earlier verdict is held back until a new check runs.
Premisecitation
§ Changing correlations between features and parameters
Correlations among system components in degenerate systems may be altered by perturbations although the system behavior is maintained.
“But, correlations among system components in degenerate systems may be altered by perturbations although the system behavior is maintained [63].”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [63] More-Potdar, 2026, Long-term neuromodulatory effects on the ionic current parameter space of oscillatory neurons, BioRxiv source
  Checked before — its earlier verdict is held back until a new check runs.
Premisecitation
§ Conclusions
Modifications of the voltage-dependence of one current can result in changes of the contribution of many or all of the currents in the model neuron to its behavior.
“Modifications of the voltage-dependence of one current can result in changes of the contribution of many or all of the currents in the model neuron to its behavior.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [35] Huang, 2026, Sensitivity of a model oscillator to shifts in the voltage-dependence of one or more ionic currents, J Neurophysiol source
  Checked before — its earlier verdict is held back until a new check runs.
Premisecitation
§ Conclusions
The resulting class of models, recurrent mechanistic models (RMMs), can be trained during an electrophysiology experiment.
“The resulting class of models, recurrent mechanistic models (RMMs)-can be trained during an electrophysiology experiment.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [48] Burghi, 2025, Rapid, interpretable data-driven models of neural dynamics using recurrent mechanistic models, Proc Natl Acad Sci U S A source
  Checked before — its earlier verdict is held back until a new check runs.
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
When the maximal conductance of one of the Ca2+ currents is decreased to 75%, a striking difference in behavior is revealed.
“When the maximal conductance of one of the Ca 2+ currents is decreased, even a modest decrease to 75% reveals a striking difference in behavior.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [38] Kenngott, 2026
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Interpretationreasoning
§ Degenerate, multiple solutions in neuronal behavior
Apparent failures to replicate may actually be a direct consequence of the degenerate states found in what appear to be similar control animals and preparations.
“These may look like 'failures to replicate' but are actually a direct consequence of the degenerate states found in what appear to be similar control animals and preparations.”
Quote in the paperSubstantial claim
Premisecitation
§ Conclusions
Nociceptors can achieve similar excitability using different combinations of Na(V)1.3, Na(V)1.7, and Na(V)1.8 channels.
“the authors argue that nociceptors can achieve similar excitability using different combinations of Na(V)1.3,Na(V)1.7, and Na(V)1.8channels.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [19] Xie, 2024, Similar excitability through different sodium channels and implications for the analgesic efficacy of selective drugs, eLife source
  Checked before — its earlier verdict is held back until a new check runs.
Interpretationreasoning
§ Changing correlations between features and parameters
Averaging across samples with displaced peaks of activity can produce a mean that does not capture the activity profile of any of the samples.
“When these samples are averaged, the mean shows two peaks of activity that do not capture the activity profile of any of the samples that were used to calculate the mean.”
Quote in the paperSubstantial claim
Interpretationreasoning
§ Degenerate, multiple solutions in neuronal behavior
If one investigator studied the control and 50% cases, and a second investigator studied the same control but the 75% or 25% case, this would appear as a 'failure to replicate'.
“If one investigator studied the control and 50% cases, and a second investigator studied the same control, but the 75% or 25% case, this would appear as a 'failure to replicate'.”
Quote in the paperSubstantial claim

May combine two claims. 13
Classified as probably not a substantial claim. 19

May combine two claims.
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
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.”
Quote in the paperSubstantial claim3 of 5 sources checked
- cites [32] Goldman, 2001, Global structure, robustness, and modulation of neuronal models, J Neurosci source
- cites [33] Golowasch, 2002, Failure of averaging in the construction of a conductance-based neuron model, J Neurophysiol source
- cites [35] Huang, 2026, Sensitivity of a model oscillator to shifts in the voltage-dependence of one or more ionic currents, J Neurophysiol source
- cites [36] Mondal, 2025, Relative timescale of channel voltage dependence and channel density regulation impacts assembly and recovery of activity, eLife source
- cites [37] Mondal, 2026, Persistent adaptation through dual-timescale regulation of ion channel properties, Proc Natl Acad Sci U S A source
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation
§ Introduction
Numerous reports that decry failures to replicate findings in behavioral and clinical neuroscience have triggered increased emphasis on the importance of replication.
“Numerous reports that decry failures to replicate findings in behavioral and clinical neuroscience have triggered increased emphasis on the importance of replication [1-5].”
Quote in the paperNot a substantial claim5 of 5 sources checked
- cites [1] Ioannidis, 2005, Why most published research findings are false, PLoS Med source
  In “Modeling the Framework for False Positive Findings” (page not provided), Ioannidis describes a high rate of nonreplication and criticizes treating a single statistically significant study as conclusive. “How Can We Improve the Situation?” urges attention to the totality of evidence. The paper does not establish that reports specifically in behavioral and clinical neuroscience triggered an increased emphasis on replication. (LLM, conf=0.82)
  Experimental — accuracy not yet measured
- cites [2] Crawford, 2023, From methods to monographs: fostering a culture of research quality, eNeuro source
  The Scientific Ecosystem > Publishing norms discusses inadequate reporting in neurologic research, and NINDS Efforts > Publications describes responses focused on reporting guidelines. The available passages do not say that numerous reports of failed replication in behavioral and clinical neuroscience prompted greater emphasis on replication itself (searched: failed replication, reproducibility, and renewed attention to replication). Page numbers were not available in our copy. (LLM, conf=0.72)
  Experimental — accuracy not yet measured
- cites [3] Koroshetz, 2020, Framework for advancing rigorous research, eLife source
  The Abstract (page not provided) calls for greater rigor in life and biomedical research and describes a neuroscience-focused workshop on improving research practices. It does not say that numerous reports of failed replications in behavioral and clinical neuroscience triggered an increased emphasis on replication. (LLM, conf=0.73)
  Experimental — accuracy not yet measured
- cites [4] Silberberg, 2017, Shake up conferences, Nature source
  The opening passage (labelled Abstract in our copy; page unavailable) says that much has been written about promoting rigour and reproducibility, supporting the general point that these have received attention. It does not say that reports of failed replications in behavioral and clinical neuroscience triggered that attention; searches for those terms found no such passage. (LLM, conf=0.78)
  Experimental — accuracy not yet measured
- cites [5] Haven, 2026, Reproducibility failure in biomedical research: problems and solutions, Annu Rev Med source
  The passage labeled “acknowledgments / literature cited” (page unavailable) says low replication success raised concerns about a crisis and prompted journals, funders, and others to put reproducibility more prominently on their agendas. It discusses biomedical research broadly, however, and does not specifically establish this sequence for behavioral and clinical neuroscience. (LLM, conf=0.84)
  Experimental — accuracy not yet measured
Classified as probably not a substantial claim.
Premisecitation
§ Conclusions
Populations of excitatory and inhibitory cortical neuron models replicate similar electrophysiological features despite their variable underlying parameters.
“They generated populations of excitatory and inhibitory cortical neuron models that replicate similar electrophysiological features despite their variable underlying parameters.”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [20] Reva, 2025, Higher-order interactions in neuronal function: from genes to ionic currents in biophysical models, Proc Natl Acad Sci U S A source
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisereasoning
§ Degenerate, multiple solutions in neuronal behavior
There are attempts to develop new methods to characterize the parameters of biological neurons to estimate or evaluate their contributions to neuronal dynamics.
“Therefore, there are attempts to develop new methods to characterize the parameters of biological neurons to estimate or evaluate their contributions to neuronal dynamics [48][49][50].”
Quote in the paperNot a substantial claim3 of 3 sources checked
- cites [48] Burghi, 2025, Rapid, interpretable data-driven models of neural dynamics using recurrent mechanistic models, Proc Natl Acad Sci U S A source
- cites [49] Burghi, 2025, Quantitative prediction of intracellular dynamics and synaptic currents in a small neural circuit, Front Comput Neurosci source
- cites [50] Brandoit, 2026, Fast reconstruction of degenerate populations of conductance-based neuron models from spike times, PLoS Comput Biol source
- Rests on an assumption: In experimental studies, one does not have access to all of the factors that contribute to an outcome.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation
§ Changing correlations between features and parameters
It is common for investigators to look for correlations between the expression of individual components or features to obtain insight into how individual system components contribute to system behavior.
“It is common for investigators to look for correlations between the expression of individual components or features to obtain insight into how individual system components contribute to system behavior [26,[60][61][62].”
Quote in the paperNot a substantial claim3 of 3 sources checked
- cites [26] Schulz, 2007, Quantitative expression profiling of identified neurons reveals cell-specific constraints on highly variable levels of gene expression, Proc Natl Acad Sci U S A source
- cites [60] O'Leary, 2013, Correlations in ion channel expression emerge from homeostatic tuning rules, Proc Natl Acad Sci U S A source
- cites [61] Amendola, 2012, Ca2+/cAMP-sensitive covariation of IA and IH voltage dependences tunes rebound firing in dopaminergic neurons, J Neurosci source
May combine two claims.
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
In model neuron A there is virtually no A current, while in model neuron B the A current is quite large.
“Note that in model neuron A there is virtually no A current (purple), while in model neuron B the A current is quite large.”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [42] Alonso, 2019, Visualization of currents in neural models with similar behavior and different conductance densities, eLife source
  In Results, under “The maximal conductances do not fully predict the currentscapes” (page unavailable), the paper reports that A-current contributions differ among its model bursters. It does not state that model A has virtually no A current while model B has a large A current, so the specific comparison is not verified by our copy. (LLM, conf=0.76)
  Experimental — accuracy not yet measured
May combine two claims.
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
Models A and B show similar behavior under control conditions, but the contributions of different currents to their control activity are different.
“While Models A and B show similar behavior under control conditions, the contributions of different currents to their control activity are different.”
Quote in the paperSubstantial claim1 of 1 sources checked
- cites [42] Alonso, 2019, Visualization of currents in neural models with similar behavior and different conductance densities, eLife source
May combine two claims.
Findingown data
§ Lack of stationarity in the environment and subject populations can produce failures to replicate
Features of our initial experimental design or assumptions about the stationarity of the world or our laboratory conditions were unfounded.
“As we investigated further, we discovered features of our initial experimental design or assumptions about the stationarity of the world or our laboratory conditions that were unfounded.”
Quote in the paperSubstantial claim
May combine two claims.
Findingcitation
§ Degenerate, multiple solutions in neuronal behavior
At 22°C, the two models in Figure 1 produce essentially the same output, illustrating a degenerate solution.
“At 22 • C the two models produce essentially the same output, and illustrate a degenerate solution.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [38] Kenngott, 2026
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Classified as probably not a substantial claim.
Findingreasoning
§ Lack of stationarity in the environment and subject populations can produce failures to replicate
My laboratory has sometimes failed to replicate an aspect of our previous work.
“My laboratory has sometimes failed to replicate an aspect of our previous work.”
Quote in the paperSubstantial claim
May combine two claims.
Interpretationreasoning
§ Molecular and analysis tools, genetic strains, and preprint servers ensure that replication across the international scientific community occurs automatically
These 'implementation checks' serve as self-correction mechanisms within the community, and alert scientists to problematic technical issues.
“These 'implementation checks' serve as self-correction mechanisms within the community, and alert scientists to problematic technical issues.”
Quote in the paperSubstantial claim
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation
§ 54 *
Simple rules can generate the complexity of biological synaptic organization.
“They suggest that simple rules can generate the complexity of biological synaptic organization.”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [23] Sorokina, 2026, Protein trafficking and synaptic demand configure complex and dynamic synaptome architectures of individual neurons, Sci Rep source
  Checked before — its earlier verdict is held back until a new check runs.
May combine two claims.
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
As temperature is changed, notable differences in the models' performance can be seen: the left-hand model loses its rhythmic activity at both 7°C and 27°C, whereas the right-hand model maintains rhythmicity over this entire temperature range.
“Nonetheless, as the temperature is changed, notable differences in the models' performance can be seen, as the left-hand model loses its rhythmic activity at both 7 • C and 27 • C, whereas the right-hand model is more resilient and maintains rhythmicity over this entire temperature range.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [38] Kenngott, 2026
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
At 22°C, the two Morris-Lecar models perform almost identically, and can therefore be viewed as degenerate solutions.
“Note that at 22 • C, the models perform almost identically, and therefore can be viewed as degenerate solutions.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [38] Kenngott, 2026
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Classified as probably not a substantial claim.
Interpretationreasoning
§ Degenerate, multiple solutions in neuronal behavior
The figure illustrates hidden complexities and challenges posed by degenerate systems.
“This figure illustrates hidden complexities and challenges posed by degenerate systems.”
Quote in the paperSubstantial claim
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationreasoning
§ Lack of stationarity in the environment and subject populations can produce failures to replicate
Changes in human health and habits over time can easily contribute to failures of replication in clinical trials.
“Similarly, changes in human health and habits over time can easily contribute to failures of replication in clinical trials.”
Quote in the paperNot a substantial claim
May combine two claims.
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
At 50% of the calcium conductance, the two models again look similar, but as the calcium conductance is further decreased, the behaviors of the models again diverge.
“Interestingly, at 50% of the calcium conductance the two models again look similar, but as the calcium conductance is further decreased, the behaviors of the models again diverge.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [38] Kenngott, 2026
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation
§ 54 *
A population of proteins, including those present at the synapse, are exceptionally long-lived.
“Recent work has identified a population of proteins, including those present at the synapse that are exceptionally long-lived, and suggest sex and experiencedependent changes in the expression of some of these long-lived proteins.”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [24] Heo, 2026, Sex- and experience-dependent regulation of synaptic protein turnover, Proc Natl Acad Sci U S A source
  Checked before — its earlier verdict is held back until a new check runs.
Classified as probably not a substantial claim.
Premisecitation
§ 54 *
The authors of this study argue that they saw no difference in their results at the two temperatures.
“The authors of this study argue that they saw no difference in their results at the two temperatures but do not show the data at the two temperatures, so the etiology of the failure to replicate remains unclear.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [54] Chen, 2026, A reassessment of NMDA receptor-dependent presynaptic homeostatic plasticity, Proc Natl Acad Sci U S A source
Probably not a substantial claim: may not pass S2 (checkable), S4 (based).
Interpretationreasoning
§ Conclusions
The mechanism has direct implications for clinical management of pain.
“This is a wonderful example of a degenerate mechanism with direct implications for clinical management of pain.”
Quote in the paperNot a substantial claim
May combine two claims.
Premisecitation
§ Conclusions
In this model, channel density and the voltage-dependence of ion channels are both regulated to maintain stable performance of a model neuron.
“In this model, channel density and the voltage-dependence of ion channels are both regulated to maintain stable performance of a model neuron.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [36] Mondal, 2025, Relative timescale of channel voltage dependence and channel density regulation impacts assembly and recovery of activity, eLife source
  Checked before — its earlier verdict is held back until a new check runs.
Classified as probably not a substantial claim.
Premisecitation
§ 54 *
The authors do not show the data at the two temperatures.
“The authors of this study argue that they saw no difference in their results at the two temperatures but do not show the data at the two temperatures, so the etiology of the failure to replicate remains unclear.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [54] Chen, 2026, A reassessment of NMDA receptor-dependent presynaptic homeostatic plasticity, Proc Natl Acad Sci U S A source
Classified as probably not a substantial claim. May combine two claims.
Premisecitation
§ 54 *
This is a report of a failure to replicate in which numerous details of experimental design were slightly different, including recording temperature (one group having used RT and the other 35C).
“This is a report of a failure to replicate in which numerous details of experimental design were slightly different, including recording temperature (one group having used RT and the other 35C.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [54] Chen, 2026, A reassessment of NMDA receptor-dependent presynaptic homeostatic plasticity, Proc Natl Acad Sci U S A source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation
§ Failure of averaging
Averaging need not fail, and the average properties of multiple neurons within a functional circuit may be an excellent predictor of the circuit's function.
“Of course, averaging need not fail, and the average properties of multiple neurons within a functional circuit may be an excellent predictor of the circuit's function [31].”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [31] Dopp, 2026, Conductance relationships across compartments associated with bursting output in a model of a motor neuron in the crustacean cardiac ganglion, J Neurophysiol source
  Checked before — its earlier verdict is held back until a new check runs.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation
§ Degenerate, multiple solutions in neuronal behavior
The Morris-Lecar model has only two voltage-dependent currents: an inward Ca2+ current that depolarizes the cell, and an outward K+ current that hyperpolarizes it.
“The Morris-Lecar model has only two voltagedependent currents, an inward Ca 2+ current that depolarizes the cell, and an outward K + current that hyperpolarizes it.”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [39] Morris, 1981, Voltage oscillations in the barnacle giant muscle fiber, Biophys J source
  Checked before — its earlier verdict is held back until a new check runs.
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Premisecitation
§ Conclusions
The speed and performance of the training methods of teacher forcing, multiple shooting, and generalized teacher forcing are tailored to data-driven models with explicit membrane voltage variables.
“The speed and performance of the training methods of teacher forcing, multiple shooting, and generalized teacher forcing are tailored to data-driven models with explicit membrane voltage variables.”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [49] Burghi, 2025, Quantitative prediction of intracellular dynamics and synaptic currents in a small neural circuit, Front Comput Neurosci source
  Checked before — its earlier verdict is held back until a new check runs.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation
§ 54 *
Stable spine dynamics, with subsets of synapses persisting for months.
“They see stable spine dynamics, with subsets of synapses persisting for months.”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [24] Heo, 2026, Sex- and experience-dependent regulation of synaptic protein turnover, Proc Natl Acad Sci U S A source
  Checked before — its earlier verdict is held back until a new check runs.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation
§ 54 *
There are sex and experience-dependent changes in the expression of some of these long-lived proteins.
“Recent work has identified a population of proteins, including those present at the synapse that are exceptionally long-lived, and suggest sex and experiencedependent changes in the expression of some of these long-lived proteins.”
Quote in the paperNot a substantial claim0 of 1 sources checked
- cites [24] Heo, 2026, Sex- and experience-dependent regulation of synaptic protein turnover, Proc Natl Acad Sci U S A source
  Checked before — its earlier verdict is held back until a new check runs.
Classified as probably not a substantial claim.
Premisecitation
§ 54 *
A combination of molecular transport mechanisms and local synaptic demand for proteins was sufficient to account for complex profiles of synaptic protein distributions in different cell types.
“They argue that a combination of molecular transport mechanisms and local synaptic demand for proteins was sufficient to account for complex profiles of synaptic protein distributions in different cell types.”
Quote in the paperSubstantial claim0 of 1 sources checked
- cites [23] Sorokina, 2026, Protein trafficking and synaptic demand configure complex and dynamic synaptome architectures of individual neurons, Sci Rep source
  Checked before — its earlier verdict is held back until a new check runs.

29 of 29

The paper relies on this without support.
Most failures to replicate have no malign etiology, but are a consequence of dedicated scientists working at the frontiers of knowledge.
“While some failures to replicate may reflect shoddy research practices, most have no malign etiology, but are a consequence of dedicated scientists working at the frontiers of knowledge.”
The paper relies on this without support.
Research practices are continuously evolving, and important errors are unlikely to go undiscovered for long.
“Research practices are continuously evolving, and important errors are unlikely to go undiscovered for long.”
The paper relies on this without support.
Labs working on worms, flies, mice, and rats routinely share reagents, methods, protocols, genetic strains, and regularly pool data.
“Labs working on worms, flies, mice, and rats routinely share reagents, methods, protocols, genetic strains, and regularly pool data.”
The paper relies on this without support.
It is becoming common for laboratories to post their 'completed' manuscripts on preprint servers such as BioRxiv.
“It is becoming common for laboratories to post their 'completed' manuscripts on preprint servers such as BioRxiv.”
The paper relies on this without support.
These preprints can be easily updated and revised, and comments arising from the international community serve as an organic community selfcorrecting mechanism.
“These preprints can be easily updated and revised, and comments arising from the international community serve as an organic community selfcorrecting mechanism.”
The paper relies on this without support.
Substantial differences in laboratory practices can inadvertently creep into study designs.
“While journals attempt to remove uncertainties relevant to experimental protocols by requiring that methodologies be carefully specified, substantial differences in laboratory practices can nonetheless inadvertently creep into study designs.”
The paper relies on this without support.
Individuals, including humans, may respond similarly to many environmental conditions, but their differences may be revealed by specific environmental stimuli or stressors.
“Individuals, including humans, may respond similarly to many environmental conditions, but their differences may be revealed by specific environmental stimuli or stressors.”
The paper relies on this without support.
The Morris-Lecar models are representative of biological neurons (or degenerate biological systems).
“This simple example predicts that apparent failures to replicate will often appear in degenerate systems.”
The paper relies on this without support.
Degeneracy is common in biological systems.
“This simple example predicts that apparent failures to replicate will often appear in degenerate systems.”
The paper relies on this without support.
In experimental studies, one does not have access to all of the factors that contribute to an outcome.
“Unfortunately, in experimental studies, one does not have access to all of the factors that contribute to an outcome.”
The paper relies on this without support.
Failures to replicate can occur when two or more groups intend to do the 'same' experiment, but do not.
“Failures to replicate can occur when two or more groups intend to do the 'same' experiment, but do not.”
The paper relies on this without support.
More consortia are pooling large data sets generated across the globe.
“Happily, more consortia are pooling large data sets generated across the globe.”
The paper relies on this without support.
These large data sets provide statistical power often lacking twenty and thirty years ago, and often better represent the diversity of the human race.
“These large data sets provide statistical power often lacking twenty and thirty years ago, and often better represent the diversity of the human race.”
The paper relies on this without support.
Most homeostatic models of intrinsic excitability published previously have regulated channel density.
“Most homeostatic models of intrinsic excitability published previously have regulated channel density.”

14 of 14

Why Most Published Research Findings Are False
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Voltage oscillations in the barnacle giant muscle fiber
Morris, C., & Lecar, H. (1981) · Biophysical Journal · doi:10.1016/s0006-3495(81)84782-0 · Cited by 2,302 · see citing works
Similar network activity from disparate circuit parameters
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Self-citation
Variable channel expression in identified single and electrically coupled neurons in different animals
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Self-citation
Global structure, robustness, and modulation of neuronal models
Goldman, M. S., Golowasch, J., Marder, E., & Abbott, L. F. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-14-05229.2001 · Cited by 371 · see citing works
Self-citation
A small-systems approach to motor pattern generation
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Failure of averaging in the construction of a conductance-based neuron model
Golowasch, J., Goldman, M. S., Abbott, L. F., & Marder, E. (2002) · Journal of Neurophysiology · doi:10.1152/jn.00412.2001 · Cited by 290 · see citing works
Self-citation
Quantitative expression profiling of identified neurons reveals cell-specific constraints on highly variable levels of gene expression
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Self-citation
How multiple conductances determine electrophysiological properties in a multicompartment model
Taylor, A. L., Goaillard, J.-M., & Marder, E. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4438-08.2009 · Cited by 202 · see citing works
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Robustness of burst firing in dissociated purkinje neurons with acute or long-term reductions in sodium conductance
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Running hot and cold: behavioral strategies, neural circuits, and the molecular machinery for thermotaxis in C. elegans and Drosophila
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Correlations in ion channel expression emerge from homeostatic tuning rules
O'Leary, T., Williams, A. H., Caplan, J. S., & Marder, E. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1309966110 · Cited by 192 · see citing works
Self-citation
Precise temperature compensation of phase in a rhythmic motor pattern
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Self-citation
How Caenorhabditis elegans Senses Mechanical Stress, Temperature, and Other Physical Stimuli
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Robustness of a rhythmic circuit to short- and long-term temperature changes
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Self-citation
Visualization of currents in neural models with similar behavior and different conductance densities
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Self-citation
A kinetic map of the homomeric voltage-gated potassium channel (Kv) family
Ranjan, R., Logette, E., Marani, M., Herzog, M., Tâche, V., Scantamburlo, E., Buchillier, V., & Markram, H. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00358 · Cited by 116 · see citing works
A brain atlas of synapse protein lifetime across the mouse lifespan
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Neuropeptide modulation of microcircuits
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Climate change and disorders of the nervous system
Sisodiya, S. M., Gulcebi, M. I., Fortunato, F., Mills, J. D., Haynes, E., Bramon, E., Chadwick, P., Ciccarelli, O., David, A. S., De Meyer, K., et al. (2024) · The Lancet Neurology · doi:10.1016/s1474-4422(24)00087-5 · Cited by 105 · see citing works
Correlations in ion channel mRNA in rhythmically active neurons
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Self-citation
Ca 2+ /cAMP-Sensitive Covariation of I A and I H Voltage Dependences Tunes Rebound Firing in Dopaminergic Neurons
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Deep sequencing of transcriptomes from the nervous systems of two decapod crustaceans to characterize genes important for neural circuit function and modulation
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Self-citation
Temperature compensation in a small rhythmic circuit
Alonso, L. M., & Marder, E. (2020) · eLife · doi:10.7554/elife.55470 · Cited by 86 · see citing works
Self-citation
A quantitative study of potassium channel kinetics in rat skeletal muscle from 1 to 37 degrees C
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Different Sensory Systems Share Projection Neurons But Elicit Distinct Motor Patterns
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Phase maintenance in a rhythmic motor pattern during temperature changes in vivo
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The extraordinary AFD thermosensor of C. elegans
Goodman, M. B., & Sengupta, P. (2018) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-2089-5 · Cited by 69 · see citing works
A biophysical perspective on the resilience of neuronal excitability across timescales
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Self-citation
A newly identified extrinsic input triggers a distinct gastric mill rhythmviaactivation of modulatory projection neurons
Blitz, D. M., White, R. S., Saideman, S. R., Cook, A. P., Christie, A. E., Farzan Nadim, A., & Nusbaum, M. P. (2008) · Journal of Experimental Biology · doi:10.1242/jeb.015222 · Cited by 57 · see citing works
From the neuroscience of individual variability to climate change
Marder, E., & Rue, M. C. P. (2021) · The Journal of Neuroscience · doi:10.1523/jneurosci.1261-21.2021 · Cited by 50 · see citing works
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Neuropeptide Receptor Transcript Expression Levels and Magnitude of Ionic Current Responses Show Cell Type-Specific Differences in a Small Motor Circuit
Garcia, V. J., Daur, N., Temporal, S., Schulz, D. J., & Bucher, D. M. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0171-15.2015 · Cited by 44 · see citing works
Homeostatic regulation of neuronal function: importance of degeneracy and pleiotropy
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The brain's best kept secret is its degenerate structure
Albantakis, L., Bernard, C., Brenner, N., Marder, E., & Narayanan, R. (2024) · The Journal of Neuroscience · doi:10.1523/jneurosci.1339-24.2024 · Cited by 34 · see citing works
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Molecular profiling of single neurons of known identity in two ganglia from the crab Cancer borealis
Northcutt, A. J., Kick, D. R., Otopalik, A. G., Goetz, B. M., Harris, R. M., Santin, J. M., Hofmann, H. A., Marder, E., & Schulz, D. J. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1911413116 · Cited by 33 · see citing works
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Similar excitability through different sodium channels and implications for the analgesic efficacy of selective drugs
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Causal composition: Structural differences among dynamically equivalent systems
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Framework for advancing rigorous research
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Mapping circuit dynamics during function and dysfunction
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Gating of homeostatic regulation of intrinsic excitability produces cryptic long-term storage of prior perturbations
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From methods to monographs: fostering a culture of research quality
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Homeostatic plasticity of excitability in crustacean central pattern generator networks
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Hot brain: practical climate change advice for neurologists
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Repeated applications of high potassium elicit long-term changes in a motor circuit from the crab, Cancer borealis
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Resilience of circuits to environmental challenge
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Similar excitability through different sodium channels and implications for the analgesic efficacy of selective drugs
Xie, Y., Yang, J., Ratté, S., & Prescott, S. A. (2023) · eLife · doi:10.7554/elife.90960 · Cited by 12 · see citing works
Degeneracy rules
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Shake up conferences
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Thermal acclimation and habitat-dependent differences in temperature robustness of a crustacean motor circuit
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Reproducibility failure in biomedical research: problems and solutions
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Ih block reveals separation of timescales in pyloric rhythm response to temperature changes in Cancer borealisPreprint
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Ih block reveals separation of timescales in pyloric rhythm response to temperature changes in Cancer borealis
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Room Temperature in Scientific Protocols and Experiments Should be Defined: a Reproducibility Issue
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Muscles innervated by a single motor neuron exhibit divergent synaptic properties on multiple time scales
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Rapid, interpretable data-driven models of neural dynamics using recurrent mechanistic models
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Sex- and experience-dependent regulation of synaptic protein turnover
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Higher-order interactions in neuronal function: from genes to ionic currents in biophysical models
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Persistent adaptation through dual-timescale regulation of ion channel properties
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Self-citation
The problem with one-size-fits-all medicine: biological sex and the aging immune system
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Relative timescale of channel voltage dependence and channel density regulation impacts assembly and recovery of activity
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Self-citation
Quantitative prediction of intracellular dynamics and synaptic currents in a small neural circuit
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Self-citation
Protein trafficking and synaptic demand configure complex and dynamic synaptome architectures of individual neurons
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Temperature and pH-dependent potassium currents of muscles of the stomatogastric nervous system of the crab, Cancer borealis
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Self-citation
A reassessment of NMDA receptor-dependent presynaptic homeostatic plasticity
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An unusual potassium conductance protects Caenorhabditis elegans pharyngeal muscle rhythms against environmental noise
Kenngott, M., Sengupta, P., Lockery, S., & Marder, E. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2422709122 · Cited by 1 · see citing works
Self-citation
Fast reconstruction of degenerate populations of conductance-based neuron models from spike times
Brandoit, J., Ernst, D., Drion, G., & Fyon, A. (2026) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1014337 · Cited by 1 · see citing works
Conductance relationships across compartments associated with bursting output in a model of a motor neuron in the crustacean cardiac ganglion
Dopp, D. P., Samarth, P. S., Wang, J., Kick, D. R., Schulz, D. J., & Nair, S. S. (2026) · Journal of Neurophysiology · doi:10.1152/jn.00324.2024 · Cited by 1 · see citing works
Sensitivity of a model oscillator to shifts in the voltage-dependence of one or more ionic currents
Huang, I., Alonso, L. M., & Marder, E. (2026) · Journal of Neurophysiology · doi:10.1152/jn.00055.2026 · Cited by 1 · see citing works
Self-citation
Quantitative Neuropeptidomics Reveals Thermal Acclimation-Induced Remodeling of Peptidergic Signaling in the American Lobster Homarus americanus
Tran, V. N. H., Kedia, S., Lu, G., Selby, K. G., Duong, T., Del Mundo, Z., Marder, E., & Li, L. (2026) · doi:10.64898/2026.03.07.710231 · Cited by 1
Self-citation
Long-term neuromodulatory effects on the ionic current parameter space of oscillatory neurons
More-Potdar, S., & Golowasch, J. (2026) · doi:10.64898/2026.02.22.707287
Compensation of the effects of temperature on a motor system in the crab, Cancer borealis
Jacquerie, K., DiMartino, J. M., Dalal, A., Zeng, J., & Marder, E. (2026) · doi:10.64898/2026.06.23.734078
Self-citation
Temperature and pH-dependent Potassium Currents of Muscles of the Stomatogastric Nervous System of the Crab, Cancer borealis
Jacquerie, K., Poghosyan, A., Schulz, D. J., & Marder, E. (2025) · doi:10.1101/2025.10.06.680680
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Research works printed but not linked: 3

Nusbaum, 1999, The role of cotransmitters and peptidase activity in shaping the actions of peptidergic neurons, Soc Neurosci Abstr, 25, 1967
Kiani, 2025, Room temperature: understanding the importance and impact, J Phys Chem Biophys, 15, 434
Gulcebi, 2025, Imperatives and co-benefits of resesarch into climate change and neurology, Nat Rev Neurol, 1

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Authors: Marder, E.
Affiliations: Brandeis University (US)
Corresponding author: Marder, Eve
ORCID: Marder, Eve
Venue: Current Opinion in Neurobiology
Publisher: Elsevier BV
Published: 2026-12
Volume: 101
Pages: 103268
ISSN: 0959-4388 (ISSN-L)
DOI: 10.1016/j.conb.2026.103268
OpenAlex: W7207516324
Cited by: 0
References: 65
FWCI: 0.00
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc/4.0/ (vor)
Locations: Current Opinion in Neurobiology (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R35NS142987)
Topics: Social Sciences › Arts and Humanities › History and Philosophy of Science › Philosophy and History of Science
Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
Social Sciences › Decision Sciences › Information Systems and Management › Interdisciplinary Research and Collaboration
Keywords: replication failure, experimental design, statistical analysis

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-05.

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A feature and not a bug: Replication failures can lead to new biology

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