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Cited by 3Ion channel regulation and functionNeural dynamics and brain functionNeuroscience and Neuropharmacology Research

Persistent adaptation through dual-timescale regulation of ion channel properties

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Mondal, Yugarshi, Calabrese, Ronald L., Marder, Eve·2026·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2530340123PMC PMC12974478

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Abstract

Neurons are terminally differentiated cells that adapt to maintain stable function over years, despite encountering a wide range of environmental perturbations. In some cases, recovery from perturbation is not shaped by prior exposure; in others, recovery depends on the neuron’s perturbation history. A particularly striking form of history-dependent recovery occurs when prior exposure enhances the neuron’s ability to recover from future perturbations while leaving baseline activity largely unchanged. Among the many mechanisms that may contribute to such history-dependent improvement in recovery, we investigate one based on the regulation of intrinsic currents. Using a model of activity-dependent homeostasis, we show that improved recovery can be encoded through lasting changes in channel density, while rapid shifts in ion channel voltage-dependence provide immediate compensation during perturbations. We refer to the long-lasting intrinsic trace that accompanies this improved recovery a persistent adaptation. Interestingly, these roles are noninterchangeable: when voltage-dependence evolves slowly and maximal conductances change rapidly, an intrinsic trace is not stored, eliminating persistent adaptation even when improved recovery is preserved.

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  • 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.”

    From A feature and not a bug: Replication failures can lead to new biology (2026) · cites this paper as [37]

  • Degeneracy can be produced in models with the same types of currents, but different numbers of channels, variable sets of voltage dependences of channels, or as a function of other parameters controlling channel function.

    “Degeneracy can be produced in models with the same types of currents, but different numbers of channels [32,33], variable sets of voltage dependences of channels [35-37], or as a function of other parameters controlling channel function.”

    From A feature and not a bug: Replication failures can lead to new biology (2026) · cites this paper as [37]

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Cited by

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Authors
Mondal, Y., Calabrese, R. L., & Marder, E.
Affiliations
  • Brandeis University (US)
  • Emory University (US)
Corresponding author
Marder, Eve
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2026-03-02
Volume
123
Issue
10
Pages
e2530340123-e2530340123
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2530340123
PMC
PMC12974478
OpenAlex
W7133200915
Cited by
3
References
2
Citations by year
2026: 3
FWCI
5.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by-nc)
Funders
  • HHS | NIH | National Institute of Mental Health (5 R01 MH46742-34)
  • HHS | NIH | National Institute of Neurological Disorders and Stroke (R35NS142987-01)
  • Swartz Foundation (None)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
ion channel modulation, voltage dependence, channel density, neuroplasticity, maximal conductance

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