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Dissertation
Rhythmogenic and supraspinal recruitment mechanisms of lumbar spinal Shox2 interneurons
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2025
DOI:
https://doi.org/10.17918/00011119
Abstract
Rhythm is a critical feature of locomotion and is generated by interneurons in the lumbar spinal cord which convert tonic supraspinal commands into rhythmic motor signals. Spinal interneurons expressing the transcription factor Shox2 include a group of putatively rhythmogenic interneurons in mice. Intrinsic properties likely differentially contribute to the initiation and maintenance of rhythmic activity throughout postnatal maturation, but how these properties develop in Shox2 interneurons is unknown. Furthermore, excitatory neurons in the lateral paragigantocellular nucleus (LPGi) are robustly locomotor-promoting via their spinal projections. Shox2 interneurons are poised to be an entry point for supraspinal input into the locomotor central pattern generator, but whether these neurons directly receive such input remains untested. Thus, this thesis explores intrinsic rhythmogenic properties in Shox2 interneurons throughout postnatal development, how oscillations may be generated in adult Shox2 interneurons, and the nature of the supraspinal input Shox2 interneurons receive. We identified voltage-sensitive currents and underlying ion channels possessed by Shox2 interneurons across three age groups. We show that, with increasing age, specific currents grow in magnitude and electrophysiological diversity increases. Additionally, we show that manipulating specific voltage-dependent currents and mimicking physiological conditions can lead to burst firing in adult Shox2 interneurons in the lumbar spinal slice. Lastly, we identified a functional, monosynaptic, and excitatory connection from the LPGi onto adult lumbar Shox2 interneurons. The intrinsic and connectivity properties identified here may serve as therapeutic targets for the treatment of paralysis in which mature spinal locomotor circuits are intact but lacking descending control.
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Details
- Title
- Rhythmogenic and supraspinal recruitment mechanisms of lumbar spinal Shox2 interneurons
- Creators
- Shayna Singh
- Contributors
- Kimberly J. Dougherty (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xv, 163 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Neurology; Drexel University
- Other Identifier
- 991022066754804721