Maturation of persistent and hyperpolarization-activated inward currents shapes the differential activation of motoneuron subtypes during postnatal development

  1. Simon A Sharples
  2. Gareth B Miles  Is a corresponding author
  1. University of St Andrews, United Kingdom

Abstract

The size principle underlies the orderly recruitment of motor units; however, motoneuron size is a poor predictor of recruitment amongst functionally defined motoneuron subtypes. Whilst intrinsic properties are key regulators of motoneuron recruitment, the underlying currents involved are not well defined. Whole-cell patch-clamp electrophysiology was deployed to study intrinsic properties, and the underlying currents, that contribute to the differential activation of delayed and immediate firing motoneuron subtypes. Motoneurons were studied during the first three postnatal weeks in mice to identify key properties that contribute to rheobase and may be important to establish orderly recruitment. We find that delayed and immediate firing motoneurons are functionally homogeneous during the first postnatal week and are activated based on size, irrespective of subtype. The rheobase of motoneuron subtypes become staggered during the second postnatal week, which coincides with the differential maturation of passive and active properties, particularly persistent inward currents. Rheobase of delayed firing motoneurons increases further in the third postnatal week due to the development of a prominent resting hyperpolarization-activated inward current. Our results suggest that motoneuron recruitment is multifactorial, with recruitment order established during postnatal development through the differential maturation of passive properties and sequential integration of persistent and hyperpolarization-activated inward currents.

Data availability

Source data included in all figures (Figures 2-6 + Supplemental Figure 1 2), and the Supplemental Tables have been uploaded as excel files with the manuscript.

Article and author information

Author details

  1. Simon A Sharples

    School of Psychology and Neuroscience, University of St Andrews, St Andrews, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Gareth B Miles

    School of Psychology and Neuroscience, University of St Andrews, St Andrews, United Kingdom
    For correspondence
    gbm4@st-andrews.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8624-4625

Funding

Royal Society (NIF/R1/180091)

  • Simon A Sharples

Natural Sciences and Engineering Research Council of Canada (NSERC-PDF-517295-2018)

  • Simon A Sharples

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

Reviewing Editor

  1. Robert M Brownstone, University College London, United Kingdom

Ethics

Animal experimentation: All procedures performed were conducted in accordancewith the UK Animals (Scientific Procedures) Act 1986 and were approved by the University of StAndrews Animal Welfare Ethics Committee. (PPL: P6F7B721E).

Version history

  1. Preprint posted: June 17, 2021 (view preprint)
  2. Received: June 17, 2021
  3. Accepted: November 15, 2021
  4. Accepted Manuscript published: November 16, 2021 (version 1)
  5. Version of Record published: December 3, 2021 (version 2)

Copyright

© 2021, Sharples & Miles

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.

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  1. Simon A Sharples
  2. Gareth B Miles
(2021)
Maturation of persistent and hyperpolarization-activated inward currents shapes the differential activation of motoneuron subtypes during postnatal development
eLife 10:e71385.
https://doi.org/10.7554/eLife.71385

Share this article

https://doi.org/10.7554/eLife.71385

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