Minimal requirements for a neuron to co-regulate many properties and the implications for ion channel correlations and robustness

  1. Jane Yang
  2. Husain Shakil
  3. Stéphanie Ratté
  4. Steven Alec Prescott  Is a corresponding author
  1. The Hospital for Sick Children, Canada

Abstract

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 co-regulate 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 multi-output solution set) correspond to the intersection between single-output solution sets. Properties can be effectively co-regulated 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 co-adjusted 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.

Data availability

All computer code is available at http://modeldb.yale.edu/267309 and at http://prescottlab.ca/code-for-models. Key parameter values are provided in Supplementary File 1. Other parameter values are identified in the Methods. Source data is provided for Figure 2.

Article and author information

Author details

  1. Jane Yang

    Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0114-5503
  2. Husain Shakil

    Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3995-6811
  3. Stéphanie Ratté

    Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Steven Alec Prescott

    Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Canada
    For correspondence
    steve.prescott@sickkids.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3827-4512

Funding

Canadian Institutes of Health Research (Foundation Grant 167276)

  • Steven Alec Prescott

Natural Sciences and Engineering Research Council of Canada (Discovery Grant RGPIN 436168)

  • Steven Alec Prescott

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Timothy O'Leary, University of Cambridge, United Kingdom

Ethics

Animal experimentation: All experimental procedures were approved by The Hospital for Sick Children Animal Care Committee (protocol #53451) and were conducted in accordance with guidelines from the Canadian Council on Animal Care

Version history

  1. Preprint posted: December 4, 2020 (view preprint)
  2. Received: August 6, 2021
  3. Accepted: March 3, 2022
  4. Accepted Manuscript published: March 16, 2022 (version 1)
  5. Version of Record published: April 6, 2022 (version 2)

Copyright

© 2022, Yang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,121
    views
  • 189
    downloads
  • 28
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Jane Yang
  2. Husain Shakil
  3. Stéphanie Ratté
  4. Steven Alec Prescott
(2022)
Minimal requirements for a neuron to co-regulate many properties and the implications for ion channel correlations and robustness
eLife 11:e72875.
https://doi.org/10.7554/eLife.72875

Share this article

https://doi.org/10.7554/eLife.72875

Further reading

    1. Computational and Systems Biology
    2. Neuroscience
    Andrea I Luppi, Pedro AM Mediano ... Emmanuel A Stamatakis
    Research Article

    How is the information-processing architecture of the human brain organised, and how does its organisation support consciousness? Here, we combine network science and a rigorous information-theoretic notion of synergy to delineate a ‘synergistic global workspace’, comprising gateway regions that gather synergistic information from specialised modules across the human brain. This information is then integrated within the workspace and widely distributed via broadcaster regions. Through functional MRI analysis, we show that gateway regions of the synergistic workspace correspond to the human brain’s default mode network, whereas broadcasters coincide with the executive control network. We find that loss of consciousness due to general anaesthesia or disorders of consciousness corresponds to diminished ability of the synergistic workspace to integrate information, which is restored upon recovery. Thus, loss of consciousness coincides with a breakdown of information integration within the synergistic workspace of the human brain. This work contributes to conceptual and empirical reconciliation between two prominent scientific theories of consciousness, the Global Neuronal Workspace and Integrated Information Theory, while also advancing our understanding of how the human brain supports consciousness through the synergistic integration of information.

    1. Neuroscience
    Liu Zhou, Wei Wei ... Zijiang J He
    Research Article

    We reliably judge locations of static objects when we walk despite the retinal images of these objects moving with every step we take. Here, we showed our brains solve this optical illusion by adopting an allocentric spatial reference frame. We measured perceived target location after the observer walked a short distance from the home base. Supporting the allocentric coding scheme, we found the intrinsic bias , which acts as a spatial reference frame for perceiving location of a dimly lit target in the dark, remained grounded at the home base rather than traveled along with the observer. The path-integration mechanism responsible for this can utilize both active and passive (vestibular) translational motion signals, but only along the horizontal direction. This asymmetric path-integration finding in human visual space perception is reminiscent of the asymmetric spatial memory finding in desert ants, pointing to nature’s wondrous and logically simple design for terrestrial creatures.