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A biophysical perspective on the resilience of neuronal excitability across timescales

Nature Reviews Neuroscience volume 24, pages 640–652 (2023)Cite this article

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Abstract

Neuronal membrane excitability must be resilient to perturbations that can take place over timescales from milliseconds to months (or even years in long-lived animals). A great deal of attention has been paid to classes of homeostatic mechanisms that contribute to long-term maintenance of neuronal excitability through processes that alter a key structural parameter: the number of ion channel proteins present at the neuronal membrane. However, less attention has been paid to the self-regulating ‘automatic’ mechanisms that contribute to neuronal resilience by virtue of the kinetic properties of ion channels themselves. Here, we propose that these two sets of mechanisms are complementary instantiations of feedback control, together enabling resilience on a wide range of temporal scales. We further point to several methodological and conceptual challenges entailed in studying these processes — both of which involve enmeshed feedback control loops — and consider the consequences of these mechanisms of resilience.

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Fig. 1: Resilience of excitability by feedback regulation of channel protein expression.
Fig. 2: Examples of changes in spiking behaviour owing to kinetic-based regulation of channels and receptors.
Fig. 3: A hierarchy of closed loops, operating at different timescales.
Fig. 4: Stability of the pyloric circuit of crustacean stomatogastric ganglion at extreme temperatures correlates with changes in ocean temperature.

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Acknowledgements

E.M. is supported by NIH Grants R35NS097343 and R01MH046742. S.M. is supported by grants from the Israel Science Foundation (ISF 806/19) and the Schaefer Scholars Program at Columbia University’s Vagelos College of Physicians and Surgeons.

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  1. Faculty of Medicine, Technion — Institute of Technology, Haifa, Israel

    Shimon Marom

  2. Biology Department, Brandeis University, Waltham, MA, USA

    Eve Marder

  3. Volen National Center for Complex Systems, Brandeis University, Waltham, MA, USA

    Eve Marder

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Marom, S., Marder, E. A biophysical perspective on the resilience of neuronal excitability across timescales. Nat. Rev. Neurosci. 24, 640–652 (2023). https://doi.org/10.1038/s41583-023-00730-9

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