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Properties of rhythmogenic currents in spinal Shox2 interneurons across postnatal development
Journal article   Open access   Peer reviewed

Properties of rhythmogenic currents in spinal Shox2 interneurons across postnatal development

Shayna Singh, Natalia A Shevtsova, Lihua Yao, Ilya A Rybak and Kimberly J Dougherty
The Journal of physiology, v 603(10), pp 3201-3221
01 May 2025
DOI: https://doi.org/10.1113/JP287752
PMID: 40349326
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463365View
Published, Version of Record (VoR) Open Open Access (License Unspecified)

Abstract

Action Potentials Animals Female Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Homeodomain Proteins - physiology Interneurons - physiology Locomotion Male Mice Mice, Inbred C57BL Spinal Cord - growth & development Spinal Cord - physiology
Locomotor behaviours are performed by organisms throughout life, despite developmental changes in cellular properties, neural connectivity and biomechanics. The basic rhythmic activity in the central nervous system underlying locomotion is considered to be generated via a complex interplay between network and intrinsic cellular properties. Within mature mammalian spinal locomotor circuitry, we have yet to determine which properties of spinal interneurons (INs) are critical to rhythmogenesis and how they change during development. Here, we combined whole cell patch clamp recordings, immunohistochemistry and RNAscope targeting lumbar Shox2 INs in mice, which are known to be involved in locomotor rhythm generation. Our goal was to determine the postnatal developmental expression of voltage-sensitive conductances, in addition to respective ion channels, in Shox2 INs. We show that subsets of Shox2 INs display persistent inward currents, M-type potassium currents, slow afterhyperpolarization and T-type calcium currents, which are enhanced with age. By contrast, the hyperpolarization-activated and A-type potassium currents were either found with low prevalence in subsets of neonatal, juvenile, and adult Shox2 INs or did not developmentally change. We show that Shox2 INs become more electrophysiologically diverse by juvenile and adult ages, when locomotor behaviour becomes weight-bearing. Computational modelling was used to simulate and reproduce electrophysiological experiments for representative Shox2 INs to make predictions regarding the interactions between experimentally recorded conductances and persistent inward currents, and bursting behaviour. Our results suggest a developmental shift in the magnitude of rhythmogenic ionic currents and the expression of corresponding ion channels that may be important for mature locomotor behaviour. KEY POINTS: The intrinsic and voltage-sensitive properties of locomotor-related neurons contribute to shaping and maintaining activity. Shox2 interneurons (INs), similar to many other components of locomotor circuitry, are well-characterized in the neonatal mouse. Electrophysiological recordings reveal that subsets of Shox2 INs express 'rhythmogenic properties', including persistent inward currents, M-type potassium currents and slow afterhyperpolarization, as well as corresponding ion channels/RNA. Hierarchical clustering demonstrates that developmental changes seen are related to the emergence of electrophysiological cell types, largely defined by strong rhythmogenic current expression. Our data suggest that Shox2 INs gain electrophysiological diversity with age, and that Shox2 INs from adult mice may employ enhanced voltage-sensitive conductances during rhythmic locomotor activity.

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Web of Science research areas
Neurosciences
Physiology
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