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Persistent Adaptation through Dual-Timescale Regulation of Ion Channel Properties

Created on 24 Oct 2025

Authors

Mondal, Y., Calabrese, R. L., Marder, E.

Abstract

Neurons are terminally differentiated cells that adapt to maintain stable function over years, despite encountering a wide range of environmental perturbations. Some adaptations are transient, fading once the perturbation ends. Others are persistent, continuing to influence a neuron's responses to future challenges even after baseline conditions are restored. These persistent adaptations are especially intriguing because some remain undetectable under normal conditions -- only becoming apparent upon re-exposure to a perturbation. Among the many mechanisms that may contribute to persistent adaptation, we investigate one based on the regulation of intrinsic currents. Using a computational model of activity-dependent homeostasis, we show that slow changes in channel density can encode the influence of past experience and shape future responses while rapid shifts in ion channel voltage-dependence provide immediate compensation during perturbations. Together, these dual processes tune a neuron's intrinsic excitability, enabling persistent adaptation.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 24 Oct 2025.

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