TY - JOUR TI - Minimal requirements for a neuron to coregulate many properties and the implications for ion channel correlations and robustness AU - Yang, Jane AU - Shakil, Husain AU - Ratté, Stéphanie AU - Prescott, Steven A A2 - O'Leary, Timothy A2 - Huguenard, John R A2 - Franci, Alessio VL - 11 PY - 2022 DA - 2022/03/16 SP - e72875 C1 - eLife 2022;11:e72875 DO - 10.7554/eLife.72875 UR - https://doi.org/10.7554/eLife.72875 AB - Neurons regulate their excitability by adjusting their ion channel levels. Degeneracy – achieving equivalent outcomes (excitability) using different solutions (channel combinations) – facilitates this regulation by enabling a disruptive change in one channel to be offset by compensatory changes in other channels. But neurons must coregulate many properties. Pleiotropy – the impact of one channel on more than one property – complicates regulation because a compensatory ion channel change that restores one property to its target value often disrupts other properties. How then does a neuron simultaneously regulate multiple properties? Here, we demonstrate that of the many channel combinations producing the target value for one property (the single-output solution set), few combinations produce the target value for other properties. Combinations producing the target value for two or more properties (the multioutput solution set) correspond to the intersection between single-output solution sets. Properties can be effectively coregulated only if the number of adjustable channels (nin) exceeds the number of regulated properties (nout). Ion channel correlations emerge during homeostatic regulation when the dimensionality of solution space (nin − nout) is low. Even if each property can be regulated to its target value when considered in isolation, regulation as a whole fails if single-output solution sets do not intersect. Our results also highlight that ion channels must be coadjusted with different ratios to regulate different properties, which suggests that each error signal drives modulatory changes independently, despite those changes ultimately affecting the same ion channels. KW - regulation KW - homeostasis KW - degeneracy KW - excitability KW - noise KW - ion channel JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -